Is ERCC3 p.Ile244fs (c.731del) pathogenic?

ERCC3 p.Ile244fs (c.731del) is classified Pathogenic in ERCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Very rare (popmax 6.85e-05%).

How common is ERCC3 p.Ile244fs (c.731del) in the general population?

ERCC3 p.Ile244fs (c.731del) is very rare (popmax 6.85e-05%) (gnomAD).

ERCC3 p.Ile244fs

c.731del · rs1685190008 · VCV2030008

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

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 6 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,872 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: ERCC3
Protein: p.Ile244fs
Coding: c.731del
MANE Select: NM_000122
dbSNP: rs1685190008
Type: Deletion
Location: chr2:127289428 (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.Gln586fs Pathogenic/Likely pathogenic ★★ same type
ERCC3 p.Tyr579fs Pathogenic/Likely pathogenic ★★ same type
ERCC3 p.Val193fs Pathogenic/Likely pathogenic ★★ same type
ERCC3 p.Ala562fs Pathogenic ★ same type
ERCC3 p.Asp237fs Likely pathogenic ★ same type
ERCC3 p.Cys342fs Pathogenic ★ same type
ERCC3 p.Glu288fs Pathogenic ★ same type
ERCC3 p.Glu372fs 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/ercc3-p-ile244fs (accessed [today's date]).

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