Is ERCC4 p.Ile873Val (c.2617A>G) pathogenic?

ERCC4 p.Ile873Val (c.2617A>G) is classified Benign/Likely benign in ERCC4 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0661); Low-frequency (popmax 2.03%, afr); Associated with Fanconi anemia complementation group Q.

What condition is associated with ERCC4 p.Ile873Val (c.2617A>G)?

ERCC4 p.Ile873Val (c.2617A>G) is associated with Fanconi anemia complementation group Q, xeroderma pigmentosum group F, Cockayne syndrome (ClinVar).

How common is ERCC4 p.Ile873Val (c.2617A>G) in the general population?

ERCC4 p.Ile873Val (c.2617A>G) is low-frequency (popmax 2.03%, afr) (gnomAD).

What do computational predictors say about ERCC4 p.Ile873Val (c.2617A>G)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

ERCC4 p.Ile873Val

c.2617A>G · rs2020957 · VCV134135

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia complementation group Q

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 28 kb · p 0.011 · regional, not allelic
Overall
CADD	17.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.03% African / African-American · 1,526/75,046 alleles

Filtering AF 1.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.91%

Overall 0.106% 1,705/1,614,196 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.03%	49
Remaining individualsnot grpmax-eligible	0.138%	727
Middle Eastern	0.099%	1,010
Admixed American	0.08%	1,251
South Asian	0.0121%	8,281
European (non-Finnish)	0.00237%	42,144

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: ERCC4
Protein: p.Ile873Val
Coding: c.2617A>G
MANE Select: NM_005236
dbSNP: rs2020957
Type: single nucleotide variant
Location: chr16:13948213 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 13 PDB
Residue 873: a UniProt-annotated variant site (in); an α-helix; the 'hhh2, dimerization with ercc1' region

Full ERCC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fanconi anemia complementation group Q — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group F Cockayne syndrome xeroderma pigmentosum

Similar variants

ERCC4 p.Ile873Met Uncertain significance ★ ⚠ same residue
ERCC4 p.Ile873= Likely benign ★ same residue
ERCC4 c.1102+1G>T Likely pathogenic ★★ same condition
ERCC4 c.793-2A>G Pathogenic ★★ same condition
ERCC4 p.Arg20Ter Pathogenic ★★ same condition
ERCC4 p.Arg589Trp Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Arg689Ser Likely pathogenic ★★ same condition
ERCC4 p.Arg772Ter Pathogenic/Likely pathogenic ★★ same condition

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/ercc4-p-ile873val (accessed [today's date]).

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