# NM_001983.4(ERCC1):c.864C>T (p.Val288=)

https://sugi.bio/variant/ercc1-p-val288

## Summary

**ERCC1 p.Val288= (c.864C>T)** is classified **Likely benign** in ERCC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-05-22). Very rare (popmax 0.0034%, amr); Associated with ERCC1-related disorder.

**At a glance:** Likely benign · review: No assertion criteria · rsID rs765177749 · 1 submitter · 1 linked condition · very rare (popmax 0.0034%, amr)

## For patients & families {#patients}

This is a change in the ERCC1 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to ERCC1-related disorder.

*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 | [ERCC1](https://sugi.bio/atlas/gene/ERCC1/) |
| Protein change (HGVS p.) | p.Val288= |
| Coding change (HGVS c.) | c.864C>T |
| MANE Select transcript | [NM_012099](https://www.ncbi.nlm.nih.gov/nuccore/NM_012099) (variant reported on NM_001983) |
| dbSNP | [rs765177749](https://www.ncbi.nlm.nih.gov/snp/rs765177749/) |
| Variant type | single nucleotide variant |
| Location | chr19:45409705-45409705 (GRCh38) |
| ClinVar | [VCV3036757](https://www.ncbi.nlm.nih.gov/clinvar/variation/3036757/) |

**All HGVS expressions:** `LRG_305:g.74124C>T`, `LRG_305t1:c.864C>T`, `NC_000019.10:g.45409705G>A`, `NC_000019.9:g.45912963G>A`, `NG_015839.2:g.74124C>T`, `NM_001166049.2:c.792C>T`, `NM_001297590.3:c.*204G>A`, `NM_001369412.1:c.864C>T`, `NM_001369413.1:c.864C>T`, `NM_001369414.1:c.864C>T`, `NM_001369415.1:c.864C>T`, `NM_001369416.1:c.864C>T`, `NM_001369417.1:c.792C>T`, `NM_001369418.1:c.792C>T`, `NM_001369419.1:c.792C>T`, `NM_001983.4:c.864C>T`, `NM_012099.3:c.*204G>A`

## 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 3.814, GERP 0.451, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 8.294**. 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 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 (gnomAD v4.1): grpmax **0.0034%** (amr) · FAF95 0.000564% · FAF99 0.000211% · 2/58,864 in the highest group · 3/916,186 alleles overall — very rare (popmax 0.0034%, amr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Admixed American (grpmax) | 0.0034% | 29,432 |
| Remaining individuals (not grpmax-eligible) | 0.00252% | 39,688 |

*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}

**Likely benign** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2020-05-22.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2020-05-22 |

## Associated conditions {#conditions}

[ERCC1-related disorder](https://sugi.bio/atlas/disease/ercc1-related-disorder/).

**Reported phenotype names (ClinVar):** ERCC1-related disorder, ERCC1-related condition.

### 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 3036757). 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.*