# NM_001242.5(CD27):c.479del (p.Met160fs)

https://sugi.bio/variant/cd27-p-met160fs

## Summary

**CD27 p.Met160fs (c.479del)** is classified **Pathogenic** in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). No gnomAD frequency available for this variant; Associated with lymphoproliferative syndrome 2.

**At a glance:** Pathogenic · review: Single submitter · rsID rs2498141484 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the CD27 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to lymphoproliferative syndrome 2.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Adolescent, Adult, Childhood, Infancy |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0024968/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CD27](https://sugi.bio/atlas/gene/CD27/) |
| Protein change (HGVS p.) | p.Met160fs |
| Coding change (HGVS c.) | c.479del |
| dbSNP | [rs2498141484](https://www.ncbi.nlm.nih.gov/snp/rs2498141484/) |
| Variant type | Deletion |
| Location | chr12:6450571-6450571 (GRCh38) |
| ClinVar | [VCV2825285](https://www.ncbi.nlm.nih.gov/clinvar/variation/2825285/) |

**All HGVS expressions:** `LRG_357:g.10687del`, `LRG_357t1:c.479del`, `NC_000012.11:g.6559737del`, `NC_000012.12:g.6450571del`, `NG_031995.1:g.10687del`, `NM_001242.5:c.479del`, `NM_001413263.1:c.572del`, `NM_001413264.1:c.452del`, `NM_001413265.1:c.299del`, `NM_001413266.1:c.29del`, `NM_001413267.1:c.29del`, `NM_001413268.1:c.29del`, `NR_015382.2:n.947del`, `NR_182125.1:n.625del`, `NR_182126.1:n.625del`, `NR_182127.1:n.607del`, `NR_182128.1:n.618del`

## 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 -0.199, GERP -1.77 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. For a truncating variant the loss-of-function impact is position-dependent — C-terminal / last-exon truncations may escape nonsense-mediated decay. *Descriptive; not an applied PVS1 code.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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.*

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-10-15.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Pathogenic | criteria provided, single submitter | clinical testing | 2025-10-15 |

## Associated conditions {#conditions}

[lymphoproliferative syndrome 2](https://sugi.bio/atlas/disease/lymphoproliferative-syndrome-2/).

**Reported phenotype names (ClinVar):** Lymphoproliferative syndrome 2, CD27 DEFICIENCY, Combined immunodeficiency due to CD27 deficiency.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 2825285). 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.*