Is ERCC4 p.Pro194fs (c.581del) pathogenic?

ERCC4 p.Pro194fs (c.581del) is classified Likely pathogenic in ERCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-22). Absent from gnomAD v4.1; Associated with xeroderma pigmentosum group F.

What condition is associated with ERCC4 p.Pro194fs (c.581del)?

ERCC4 p.Pro194fs (c.581del) is associated with xeroderma pigmentosum group F (ClinVar).

How common is ERCC4 p.Pro194fs (c.581del) in the general population?

ERCC4 p.Pro194fs (c.581del) is absent from gnomAD v4.1 (gnomAD).

ERCC4 p.Pro194fs

Q: How is Xeroderma pigmentosum-Cockayne syndrome complex inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.581del · rs2543169545 · VCV1709151

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,102)

Conditions

xeroderma pigmentosum group F

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 3 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,102). 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.Pro194fs
Coding: c.581del
MANE Select: NM_005236
dbSNP: rs2543169545
Type: Deletion
Location: chr16:13926752 (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 194: the 'helicase-like' region

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

Disease context

xeroderma pigmentosum group F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC4 p.Arg468fs Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Asn308fs Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Glu628fs Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Phe186fs Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Thr495fs Pathogenic ★★ same condition
ERCC4 c.1905-8_1909del Likely pathogenic ★ same condition
ERCC4 p.Ala13fs Likely pathogenic ★ same condition
ERCC4 p.Arg576_Tyr577insTer 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/ercc4-p-pro194fs (accessed [today's date]).

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