Is ERCC1 p.Val288= (c.864C>T) pathogenic?

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.

What condition is associated with ERCC1 p.Val288= (c.864C>T)?

ERCC1 p.Val288= (c.864C>T) is associated with ERCC1-related disorder (ClinVar).

How common is ERCC1 p.Val288= (c.864C>T) in the general population?

ERCC1 p.Val288= (c.864C>T) is very rare (popmax 0.0034%, amr) (gnomAD).

ERCC1 p.Val288=

c.864C>T · rs765177749 · VCV3036757

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0034%, amr)

Conditions

ERCC1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.8	GERP 0.45, phastCons 1
Overall
CADD	8.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0034% Admixed American · 2/58,864 alleles

Filtering AF 0.000564% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000327% 3/916,186 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0034%	29,432
Remaining individualsnot grpmax-eligible	0.00252%	39,688

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERCC1
Protein: p.Val288=
Coding: c.864C>T
MANE Select: NM_012099 · reported on NM_001983
dbSNP: rs765177749
Type: single nucleotide variant
Location: chr19:45409705 (GRCh38)

Full ERCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ERCC1-related disorder

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ercc1-p-val288 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown