Is ERCC5 p.Asp512= (c.1536C>T) pathogenic?

ERCC5 p.Asp512= (c.1536C>T) is classified Likely benign in ERCC5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Rare (popmax 0.165%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with ERCC5 p.Asp512= (c.1536C>T)?

ERCC5 p.Asp512= (c.1536C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ERCC5 p.Asp512= (c.1536C>T) in the general population?

ERCC5 p.Asp512= (c.1536C>T) is rare (popmax 0.165%, afr) (gnomAD).

ERCC5 p.Asp512=

c.1536C>T · rs145853933 · VCV738799

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, afr)

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 -1.1	GERP -3.4
Overall
CADD	4.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% African / African-American · 124/75,008 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.0131% 212/1,614,092 alleles · rare exomes 129/1,461,882 · genomes 83/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.165%	605
Admixed American	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0208%	4,808
South Asian	0.0176%	5,692
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00339%	29,500

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.Asp512=
Coding: c.1536C>T
MANE Select: NM_000123
dbSNP: rs145853933
Type: single nucleotide variant
Location: chr13:102862685 (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

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-asp512 (accessed [today's date]).

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