Is ERCC2 p.Leu397fs (c.1188del) pathogenic?

ERCC2 p.Leu397fs (c.1188del) is classified Pathogenic in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Absent from gnomAD.

How common is ERCC2 p.Leu397fs (c.1188del) in the general population?

ERCC2 p.Leu397fs (c.1188del) is absent from gnomAD (gnomAD).

ERCC2 p.Leu397fs

c.1188del · rs2514023304 · VCV2833726

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 12 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, 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.Leu397fs
Coding: c.1188del
MANE Select: NM_000400
dbSNP: rs2514023304
Type: Deletion
Location: chr19:45361573 (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 397: an α-helix

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

Similar variants

ERCC2 p.Leu397= Likely benign ★★ same residue
ERCC2 p.Leu397Phe Uncertain significance ★ ⚠ same residue
ERCC2 c.106-5_142del Likely pathogenic ★★ same type
ERCC2 c.1347_1377+7del Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.2047-13_2048del Likely pathogenic ★★ same type
ERCC2 c.2190+1del Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.594+2_594+5del Pathogenic/Likely pathogenic ★★ same type
ERCC2 p.Arg196_Tyr197insTer 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/ercc2-p-leu397fs (accessed [today's date]).

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