Is ERCC3 p.Glu288= (c.864G>A) pathogenic?

ERCC3 p.Glu288= (c.864G>A) is classified Likely benign in ERCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-24). Very rare (popmax 0.000508%, nfe).

How common is ERCC3 p.Glu288= (c.864G>A) in the general population?

ERCC3 p.Glu288= (c.864G>A) is very rare (popmax 0.000508%, nfe) (gnomAD).

ERCC3 p.Glu288=

c.864G>A · VCV3624311

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.16	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -2.4, phastCons 0.016
Overall
CADD	7.854	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,008 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,824 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	0.000508%	196,668

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu288=
Coding: c.864G>A
MANE Select: NM_000122
Type: single nucleotide variant
Location: chr2:127288823 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB

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

Similar variants

ERCC3 p.Glu288fs Pathogenic ★ same residue
ERCC3 c.1828-1G>C Likely pathogenic ★★ same type
ERCC3 c.471+1G>A Pathogenic ★★ same type
ERCC3 c.657+1G>A Likely pathogenic ★★ same type
ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same type
ERCC3 p.Arg195Ter Pathogenic ★★ same type
ERCC3 p.Arg234Ter Pathogenic/Likely pathogenic ★★ same type
ERCC3 p.Arg425Ter Pathogenic ★★ same type

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-glu288 (accessed [today's date]).

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