# NM_152511.5(DUSP18):c.491_492del (p.Val164fs)

https://sugi.bio/variant/dusp18-p-val164fs

## Summary

**DUSP18 p.Val164fs (c.491_492del)** is classified **Likely benign** in DUSP18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). Rare (popmax 0.53%, nfe).

**At a glance:** Likely benign · review: Single submitter · 1 submitter · rare (popmax 0.53%, nfe)

## For patients & families {#patients}

This is a change in the DUSP18 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DUSP18](https://sugi.bio/atlas/gene/DUSP18/) |
| Protein change (HGVS p.) | p.Val164fs |
| Coding change (HGVS c.) | c.491_492del |
| MANE Select transcript | [NM_152511](https://www.ncbi.nlm.nih.gov/nuccore/NM_152511) |
| Variant type | Microsatellite |
| Location | chr22:30663512-30663513 (GRCh38) |
| ClinVar | [VCV3777769](https://www.ncbi.nlm.nih.gov/clinvar/variation/3777769/) |

**All HGVS expressions:** `NC_000022.10:g.31059499CA[1]`, `NC_000022.11:g.30663512CA[1]`, `NM_001304794.2:c.491_492del`, `NM_001304795.2:c.491_492del`, `NM_001304796.2:c.*25TG[1]`, `NM_001318371.2:c.620-1979_620-1978del`, `NM_152511.5:c.491_492del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 7.617, GERP 1.29, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.984, pLI 0.10856. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in the last exon (2 of 2)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- CADD: **PHRED 26.9**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.53%** (nfe) · FAF95 0.519% · FAF99 0.514% · 6,251/1,180,046 in the highest group · 6,852/1,614,194 alleles overall — rare (popmax 0.53%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Amish (not grpmax-eligible) | 2.08% | 48 |
| European (non-Finnish) (grpmax) | 0.53% | 189 |
| Remaining individuals (not grpmax-eligible) | 0.326% | 306 |
| Admixed American | 0.255% | 392 |
| Middle Eastern | 0.215% | 466 |
| Finnish (not grpmax-eligible) | 0.153% | 653 |
| South Asian | 0.0769% | 1,301 |
| African / African-American | 0.0506% | 1,974 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.0203% | 4,934 |

Amish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**DUSP18** population constraint: LOEUF 0.984, pLI 0.10856, missense-Z 0.59778. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 92.97, 86% of residues very-high.

**1 experimental structure(s)** (PDB): [2ESB](https://www.rcsb.org/structure/2ESB).

## What this gene does {#gene-function}

*Describes the biological roles of DUSP18 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** DUSP18's established molecular role includes protein tyrosine phosphatase activity.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** protein tyrosine phosphatase activity, protein tyrosine/serine/threonine phosphatase activity, phosphatase activity.

**Biological process:** dephosphorylation, peptidyl-tyrosine dephosphorylation, peptidyl-threonine dephosphorylation.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-03-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2025-03-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related DUSP18 variant pages (same residue, condition, or type): [DUSP18 p.Val164Leu](/variant/dusp18-p-val164leu).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3777769). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*