Is ERCC2 p.Arg166fs (c.494_495insT) pathogenic?

ERCC2 p.Arg166fs (c.494495insT) is classified Pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). No gnomAD frequency available for this variant.

How common is ERCC2 p.Arg166fs (c.494_495insT) in the general population?

ERCC2 p.Arg166fs (c.494_495insT) is no gnomAD frequency available for this variant (gnomAD).

ERCC2 p.Arg166fs

c.494_495insT · rs2514034313 · VCV2650104

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 7 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.41	GERP -3, 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.Arg166fs
Coding: c.494_495insT
MANE Select: NM_000400
dbSNP: rs2514034313
Type: Insertion
Location: chr19:45364937 (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 166: the helicase atp-binding domain; a turn

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

Similar variants

ERCC2 p.Arg166His Uncertain significance ★★ ⚠ same residue
ERCC2 p.Arg166Cys Uncertain significance ★ ⚠ same residue
ERCC2 p.Arg166= Likely benign ★ same residue
ERCC2 p.Asp131Ter Likely pathogenic ★ same type
ERCC2 p.Thr460fs Likely pathogenic ★ same type
ERCC2 p.Val340fs Pathogenic ★ same type
ERCC2 p.Lys671fs Conflicting classifications of pathogenicity ★ same type
ERCC2 p.Val476fs Uncertain significance ★ 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/ercc2-p-arg166fs (accessed [today's date]).

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