Is ERCC4 c.*2139A>C pathogenic?

ERCC4 c.2139A>C is classified Likely benign in ERCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.936%, afr); Associated with xeroderma pigmentosum group F.

What condition is associated with ERCC4 c.*2139A>C?

ERCC4 c.*2139A>C is associated with xeroderma pigmentosum group F (ClinVar).

How common is ERCC4 c.*2139A>C in the general population?

ERCC4 c.*2139A>C is rare (popmax 0.936%, afr) (gnomAD).

ERCC4 c.*2139A>C

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

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

rs140019040 · VCV317851

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.936%, afr)

Conditions

xeroderma pigmentosum group F

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.68, phastCons 0.1
Non-coding constraint	Z -0.73	1 kb window · o/e 1.05 · regional · uncalibrated
Overall
CADD	12.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.936% African / African-American · 405/43,268 alleles

Filtering AF 0.861% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.831%

Overall 0.219% 423/192,786 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.936%	107
Remaining individualsnot grpmax-eligible	0.166%	604
Admixed American	0.0366%	2,733
European (non-Finnish)	0.00325%	30,753

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERCC4
Coding: c.*2139A>C
MANE Select: NM_005236
dbSNP: rs140019040
Type: single nucleotide variant
Location: chr16:13950486 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 13 PDB

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 c.1102+1G>T Likely pathogenic ★★ same condition
ERCC4 c.793-2A>G Pathogenic ★★ same condition
ERCC4 p.Arg20Ter Pathogenic ★★ same condition
ERCC4 p.Arg589Trp Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Arg689Ser Likely pathogenic ★★ same condition
ERCC4 p.Arg772Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Cys236Arg Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Cys723Ter Pathogenic/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/ercc4-c-star-2139a-c (accessed [today's date]).

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