Is ERCC2 p.Thr150fs (c.448_457del) pathogenic?

ERCC2 p.Thr150fs (c.448457del) is classified Likely pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Associated with trichothiodystrophy 1, photosensitive.

What condition is associated with ERCC2 p.Thr150fs (c.448_457del)?

ERCC2 p.Thr150fs (c.448_457del) is associated with trichothiodystrophy 1, photosensitive (ClinVar).

ERCC2 p.Thr150fs

c.448_457del · VCV4277566

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 6 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1

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

Variant & gene context

Gene: ERCC2
Protein: p.Thr150fs
Coding: c.448_457del
MANE Select: NM_000400
Type: Deletion
Location: chr19:45365062 (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 150: the helicase atp-binding domain

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 c.2047-13_2048del Likely pathogenic ★★ same condition
ERCC2 c.594+2_594+5del Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Gln662fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Phe568fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Val714fs Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Asp673fs Likely pathogenic ★ same condition
ERCC2 p.Ser140fs Likely pathogenic ★ same condition
ERCC2 p.Leu652del Conflicting classifications of pathogenicity ★ 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-thr150fs (accessed [today's date]).

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