Is ERCC4 p.Leu252fs (c.755del) pathogenic?

ERCC4 p.Leu252fs (c.755del) is classified Likely pathogenic in ERCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-29). Absent from gnomAD.

How common is ERCC4 p.Leu252fs (c.755del) in the general population?

ERCC4 p.Leu252fs (c.755del) is absent from gnomAD (gnomAD).

ERCC4 p.Leu252fs

c.755del · rs1057520104 · VCV377008

Likely pathogenic Single submitter

Classification

Likely 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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	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: ERCC4
Protein: p.Leu252fs
Coding: c.755del
MANE Select: NM_005236
dbSNP: rs1057520104
Type: Deletion
Location: chr16:13928196 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 13 PDB
Residue 252: the 'helicase-like' region; the 'leucine-zipper 1' region

Full ERCC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC4 p.Leu252= Likely benign ★ same residue
ERCC4 p.Arg468fs Pathogenic/Likely pathogenic ★★ same type
ERCC4 p.Asn308fs Pathogenic/Likely pathogenic ★★ same type
ERCC4 p.Glu628fs Pathogenic/Likely pathogenic ★★ same type
ERCC4 p.Phe186fs Pathogenic/Likely pathogenic ★★ same type
ERCC4 p.Thr495fs Pathogenic ★★ same type
ERCC4 c.1905-8_1909del Likely pathogenic ★ same type
ERCC4 p.Ala13fs Likely 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/ercc4-p-leu252fs (accessed [today's date]).

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