Is ERCC3 p.Trp77fs (c.229del) pathogenic?

ERCC3 p.Trp77fs (c.229del) is classified Pathogenic in ERCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). Absent from gnomAD.

How common is ERCC3 p.Trp77fs (c.229del) in the general population?

ERCC3 p.Trp77fs (c.229del) is absent from gnomAD (gnomAD).

ERCC3 p.Trp77fs

c.229del · rs2468070622 · VCV2696647

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: ERCC3
Protein: p.Trp77fs
Coding: c.229del
MANE Select: NM_000122
dbSNP: rs2468070622
Type: Deletion
Location: chr2:127293518 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB
Residue 77: a β-strand

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

Similar variants

ERCC3 p.Trp77Cys Uncertain significance ★ ⚠ same residue
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

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-trp77fs (accessed [today's date]).

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