Is ERCC2 p.Val476fs (c.1425_1426insAAGATCCTGGA) pathogenic?

ERCC2 p.Val476fs (c.14251426insAAGATCCTGGA) is classified Uncertain significance in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-14). Absent from gnomAD; Associated with trichothiodystrophy 1, photosensitive.

What condition is associated with ERCC2 p.Val476fs (c.1425_1426insAAGATCCTGGA)?

ERCC2 p.Val476fs (c.1425_1426insAAGATCCTGGA) is associated with trichothiodystrophy 1, photosensitive (ClinVar).

How common is ERCC2 p.Val476fs (c.1425_1426insAAGATCCTGGA) in the general population?

ERCC2 p.Val476fs (c.1425_1426insAAGATCCTGGA) is absent from gnomAD (gnomAD).

ERCC2 p.Val476fs

c.1425_1426insAAGATCCTGGA · rs1972045362 · VCV998350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

trichothiodystrophy 1, photosensitive

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 15 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.4, 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: ERCC2
Protein: p.Val476fs
Coding: c.1425_1426insAAGATCCTGGA
MANE Select: NM_000400
dbSNP: rs1972045362
Type: Insertion
Location: chr19:45357323 (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 476: the 'mediates interaction with mms19' region

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

Disease context

trichothiodystrophy 1, photosensitive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERCC2 p.Thr460fs Likely pathogenic ★ same condition
ERCC2 p.Val340fs Pathogenic ★ same condition
ERCC2 p.Lys671fs Conflicting classifications of pathogenicity ★ same condition
ERCC2 p.Val476Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
ERCC2 p.Val476Phe Uncertain significance ★ ⚠ same residue
ERCC2 c.1308-2A>G Likely pathogenic ★★ same condition
ERCC2 c.1479+2dup Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1480-2A>C Pathogenic/Likely pathogenic ★★ same condition

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-val476fs (accessed [today's date]).

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