Is ERCC2 p.Glu317Ter (c.949G>T) pathogenic?

ERCC2 p.Glu317Ter (c.949G>T) is classified Pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-30). Absent from gnomAD v4.1.

How common is ERCC2 p.Glu317Ter (c.949G>T) in the general population?

ERCC2 p.Glu317Ter (c.949G>T) is absent from gnomAD v4.1 (gnomAD).

ERCC2 p.Glu317Ter

c.949G>T · rs2514029570 · VCV2860833

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,540,740)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 23
Splicing
SpliceAI	Δ0.32	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 1
Overall
CADD	55.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,540,740). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERCC2
Protein: p.Glu317Ter
Coding: c.949G>T
MANE Select: NM_000400
dbSNP: rs2514029570
Type: single nucleotide variant
Location: chr19:45363986 (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 317: an α-helix

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

Similar variants

ERCC2 p.Glu317Asp Uncertain significance ★★ ⚠ same residue
ERCC2 c.1238-1G>C Likely pathogenic ★★ same type
ERCC2 c.1308-2A>G Likely pathogenic ★★ same type
ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.1480-2A>C Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.1544-1G>T Pathogenic/Likely 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/ercc2-p-glu317ter (accessed [today's date]).

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