Is ERCC2 p.Glu95Gly (c.284A>G) pathogenic?

ERCC2 p.Glu95Gly (c.284A>G) is classified Benign/Likely benign in ERCC2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.106); Rare (popmax 0.891%, sas); Associated with xeroderma pigmentosum group D.

What condition is associated with ERCC2 p.Glu95Gly (c.284A>G)?

ERCC2 p.Glu95Gly (c.284A>G) is associated with xeroderma pigmentosum group D, trichothiodystrophy 1, photosensitive, cerebrooculofacioskeletal syndrome 2 (ClinVar).

How common is ERCC2 p.Glu95Gly (c.284A>G) in the general population?

ERCC2 p.Glu95Gly (c.284A>G) is rare (popmax 0.891%, sas) (gnomAD).

What do computational predictors say about ERCC2 p.Glu95Gly (c.284A>G)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

ERCC2 p.Glu95Gly

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

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

c.284A>G · rs571718677 · VCV134112

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.891%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

xeroderma pigmentosum group D

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -11.80	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 17 kb · p 0.48 · regional, not allelic
Overall
CADD	25.1	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 0.891% South Asian · 811/91,044 alleles

Filtering AF 0.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.82%

Overall 0.0537% 867/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.891%	112
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Middle Eastern	0.0165%	6,060
Admixed American	0.00667%	14,997
European (non-Finnish)	0.00161%	62,103
Finnishnot grpmax-eligible	0.00156%	64,032

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: ERCC2
Protein: p.Glu95Gly
Coding: c.284A>G
MANE Select: NM_000400
dbSNP: rs571718677
Type: single nucleotide variant
Location: chr19:45368706 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 95: the helicase atp-binding domain; an α-helix

Full ERCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: trichothiodystrophy 1, photosensitive cerebrooculofacioskeletal syndrome 2 xeroderma pigmentosum

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC2 c.1238-1G>C Likely pathogenic ★★ same condition
ERCC2 c.1308-2A>G Likely pathogenic ★★ same condition
ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1480-2A>C Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1666-1G>A 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/ercc2-p-glu95gly (accessed [today's date]).

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