Is ERCC2 p.Asp131Ter (c.390_391insT) pathogenic?

ERCC2 p.Asp131Ter (c.390391insT) is classified Likely pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Absent from gnomAD; Associated with cerebrooculofacioskeletal syndrome 2.

What condition is associated with ERCC2 p.Asp131Ter (c.390_391insT)?

ERCC2 p.Asp131Ter (c.390_391insT) is associated with cerebrooculofacioskeletal syndrome 2 (ClinVar).

How common is ERCC2 p.Asp131Ter (c.390_391insT) in the general population?

ERCC2 p.Asp131Ter (c.390_391insT) is absent from gnomAD (gnomAD).

ERCC2 p.Asp131Ter

c.390_391insT · rs1199957431 · VCV3241398

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cerebrooculofacioskeletal syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 7.6	GERP 1.5, 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.Asp131Ter
Coding: c.390_391insT
MANE Select: NM_000400
dbSNP: rs1199957431
Type: Insertion
Location: chr19:45365128 (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 131: the helicase atp-binding domain; an α-helix

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

Disease context

cerebrooculofacioskeletal syndrome 2 — 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.Asp131Asn Uncertain significance ★ ⚠ same residue
ERCC2 p.Asp131Glu Uncertain significance ★ ⚠ same residue
ERCC2 p.Asp131His Uncertain significance ★ ⚠ same residue
ERCC2 p.Lys671fs Conflicting classifications of pathogenicity ★ same condition
ERCC2 p.Asp131= Likely benign ★ same residue
ERCC2 c.106-5_142del 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-asp131ter (accessed [today's date]).

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