Is ERCC5 p.Asp429= (c.1287T>C) pathogenic?

ERCC5 p.Asp429= (c.1287T>C) is classified Conflicting classifications of pathogenicity in ERCC5 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.162%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with ERCC5 p.Asp429= (c.1287T>C)?

ERCC5 p.Asp429= (c.1287T>C) is associated with hereditary neoplastic syndrome, xeroderma pigmentosum group G (ClinVar).

How common is ERCC5 p.Asp429= (c.1287T>C) in the general population?

ERCC5 p.Asp429= (c.1287T>C) is rare (popmax 0.162%, amr) (gnomAD).

ERCC5 p.Asp429=

c.1287T>C · rs146853061 · VCV310921

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.162%, amr)

Conditions

hereditary neoplastic syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.5	GERP -4.2
Overall
CADD	1.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.162% Admixed American · 97/59,928 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.111% 1,793/1,613,698 alleles · rare exomes 1,630/1,461,894 · genomes 163/151,804 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.162%	618
European (non-Finnish)	0.136%	737
Remaining individualsnot grpmax-eligible	0.0912%	1,097
Middle Eastern	0.0495%	2,021
African / African-American	0.0374%	2,673
Finnishnot grpmax-eligible	0.00782%	12,786
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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: ERCC5
Protein: p.Asp429=
Coding: c.1287T>C
MANE Select: NM_000123
dbSNP: rs146853061
Type: single nucleotide variant
Location: chr13:102862436 (GRCh38)

Full ERCC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group G

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/ercc5-p-asp429 (accessed [today's date]).

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