Is ERCC4 p.Glu482= (c.1446A>G) pathogenic?

ERCC4 p.Glu482= (c.1446A>G) is classified Benign/Likely benign in ERCC4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-31). Low-frequency (popmax 1.37%, afr); Associated with Fanconi anemia complementation group Q.

What condition is associated with ERCC4 p.Glu482= (c.1446A>G)?

ERCC4 p.Glu482= (c.1446A>G) is associated with Fanconi anemia complementation group Q, xeroderma pigmentosum group F, Cockayne syndrome (ClinVar).

How common is ERCC4 p.Glu482= (c.1446A>G) in the general population?

ERCC4 p.Glu482= (c.1446A>G) is low-frequency (popmax 1.37%, afr) (gnomAD).

ERCC4 p.Glu482=

c.1446A>G · rs114077770 · VCV415025

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, afr)

Conditions

Fanconi anemia complementation group Q

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.86	GERP -2.9
Overall
CADD	0.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.37% African / African-American · 1,020/74,432 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.27%

Overall 0.0741% 1,191/1,607,980 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.37%	73
Admixed American	0.123%	814
Middle Eastern	0.116%	862
Remaining individualsnot grpmax-eligible	0.0997%	1,003
South Asian	0.00785%	12,741
European (non-Finnish)	0.00195%	51,238

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.Glu482=
Coding: c.1446A>G
MANE Select: NM_005236
dbSNP: rs114077770
Type: single nucleotide variant
Location: chr16:13935378 (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 482: the 'disordered' 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

Similar variants

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
ERCC4 p.Cys236Arg Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Cys723Ter 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-glu482 (accessed [today's date]).

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