Is ERCC8 p.Ter397= (c.1190G>A) pathogenic?

ERCC8 p.Ter397= (c.1190G>A) is classified Likely benign in ERCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-29). Very rare (popmax 8.48e-05%, nfe).

How common is ERCC8 p.Ter397= (c.1190G>A) in the general population?

ERCC8 p.Ter397= (c.1190G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ERCC8 p.Ter397=

c.1190G>A · rs1747942027 · VCV1154446

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP 0.12, phastCons 1
Overall
CADD	7.112	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,354 alleles

Overall 6.85e-05% 1/1,460,870 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: ERCC8
Protein: p.Ter397=
Coding: c.1190G>A
MANE Select: NM_000082
dbSNP: rs1747942027
Type: single nucleotide variant
Location: chr5:60874616 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 16 PDB

Full ERCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC8 c.1041+1G>T Pathogenic/Likely pathogenic ★★ same type
ERCC8 c.1042-2A>G Pathogenic/Likely pathogenic ★★ same type
ERCC8 c.173+1119G>C Pathogenic/Likely pathogenic ★★ same type
ERCC8 c.173+1G>A Pathogenic/Likely pathogenic ★★ same type
ERCC8 c.275+1G>A Pathogenic ★★ same type
ERCC8 c.276-1G>A Likely pathogenic ★★ same type
ERCC8 c.399+1G>A Likely pathogenic ★★ same type
ERCC8 c.551-1G>A 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/ercc8-p-ter397 (accessed [today's date]).

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