Is ERCC3 p.Gln373= (c.1119G>A) pathogenic?

ERCC3 p.Gln373= (c.1119G>A) is classified Benign/Likely benign in ERCC3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele; Associated with xeroderma pigmentosum group B.

What condition is associated with ERCC3 p.Gln373= (c.1119G>A)?

ERCC3 p.Gln373= (c.1119G>A) is associated with xeroderma pigmentosum group B (ClinVar).

ERCC3 p.Gln373=

Q: How common is ERCC3 p.Gln373= (c.1119G>A) in the general population?

ERCC3 p.Gln373= (c.1119G>A) is common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Xeroderma pigmentosum-Cockayne syndrome complex inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1119G>A · rs2228544 · VCV331083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

xeroderma pigmentosum group B

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 1.4	GERP 1.2, phastCons 1
Overall
CADD	6.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.11% African / African-American · 3,833/75,048 alleles

Filtering AF 4.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.92%

Overall 0.279% 4,510/1,614,204 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.11%	20
Admixed American	0.418%	239
Middle Eastern	0.33%	303
Remaining individualsnot grpmax-eligible	0.32%	313
European (non-Finnish)	0.0168%	5,960
South Asian	0.00878%	11,386

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: ERCC3
Protein: p.Gln373=
Coding: c.1119G>A
MANE Select: NM_000122
dbSNP: rs2228544
Type: single nucleotide variant
Location: chr2:127286926 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB
Residue 373: the helicase atp-binding domain; an α-helix

Full ERCC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

xeroderma pigmentosum group B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC3 c.1828-1G>C Likely pathogenic ★★ same condition
ERCC3 c.471+1G>A Pathogenic ★★ same condition
ERCC3 c.657+1G>A Likely pathogenic ★★ same condition
ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg195Ter Pathogenic ★★ same condition
ERCC3 p.Arg425Ter Pathogenic ★★ same condition
ERCC3 p.Arg452Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg530Ter 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/ercc3-p-gln373 (accessed [today's date]).

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