Is ERCC2 p.Asp277fs (c.828_831del) pathogenic?

ERCC2 p.Asp277fs (c.828831del) is classified Pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-14). Very rare (popmax 0.000339%, nfe).

How common is ERCC2 p.Asp277fs (c.828_831del) in the general population?

ERCC2 p.Asp277fs (c.828_831del) is very rare (popmax 0.000339%, nfe) (gnomAD).

ERCC2 p.Asp277fs

c.828_831del · rs1312336997 · VCV2024178

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 0.47, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,178,594 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,457,348 alleles · very rare

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.Asp277fs
Coding: c.828_831del
MANE Select: NM_000400
dbSNP: rs1312336997
Type: Microsatellite
Location: chr19:45364104 (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 277: the helicase atp-binding domain

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

Similar variants

ERCC2 p.Asp277= Likely benign ★★ same residue
MAG p.Gly277= Likely benign ★ same residue
ERCC2 c.184-1_186del Likely pathogenic ★★ same type
ERCC2 p.Arg616fs Pathogenic/Likely pathogenic ★★ same type
ERCC2 p.Ile456del Pathogenic/Likely pathogenic ★★ same type
ERCC2 p.Ile619del Pathogenic ★★ same type
ERCC2 p.Ser630fs Pathogenic/Likely pathogenic ★★ same type
MAG c.712+19GGGGCGGGGT[2] Likely benign ★★ 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/ercc2-p-asp277fs (accessed [today's date]).

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