Is ERCC4 p.Lys601Thr (c.1802A>C) pathogenic?

ERCC4 p.Lys601Thr (c.1802A>C) is classified Conflicting classifications of pathogenicity in ERCC4 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-23). AlphaMissense: likely benign (0.1812); Rare (popmax 0.101%, afr); Associated with xeroderma pigmentosum.

What condition is associated with ERCC4 p.Lys601Thr (c.1802A>C)?

ERCC4 p.Lys601Thr (c.1802A>C) is associated with xeroderma pigmentosum, xeroderma pigmentosum group F, Fanconi anemia complementation group Q (ClinVar).

How common is ERCC4 p.Lys601Thr (c.1802A>C) in the general population?

ERCC4 p.Lys601Thr (c.1802A>C) is rare (popmax 0.101%, afr) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

What do computational predictors say about ERCC4 p.Lys601Thr (c.1802A>C)?

AlphaMissense predicts likely benign (score 0.1812) — an in-silico prediction, not a clinical call.

ERCC4 p.Lys601Thr

c.1802A>C · rs138532294 · VCV998517

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1812 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum

Computational evidence

Protein change
AlphaMissense	0.1812	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.37, phastCons 0.76
Regional constraint	o/e 1.08	unconstrained · MANE · 28 kb · p 0.011 · regional, not allelic
Overall
CADD	17.38	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% African / African-American · 76/75,000 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.00658% 106/1,611,490 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	987
Admixed American	0.0317%	3,159
Remaining individualsnot grpmax-eligible	0.0176%	5,674

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
Protein: p.Lys601Thr
Coding: c.1802A>C
MANE Select: NM_005236
dbSNP: rs138532294
Type: single nucleotide variant
Location: chr16:13935734 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group F Fanconi anemia complementation group Q Cockayne syndrome

For Xeroderma pigmentosum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

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-p-lys601thr (accessed [today's date]).

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