Is ERCC5 p.Asp379= (c.1137C>T) pathogenic?

ERCC5 p.Asp379= (c.1137C>T) is classified Likely benign in ERCC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-14). Rare (popmax 0.646%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with ERCC5 p.Asp379= (c.1137C>T)?

ERCC5 p.Asp379= (c.1137C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ERCC5 p.Asp379= (c.1137C>T) in the general population?

ERCC5 p.Asp379= (c.1137C>T) is rare (popmax 0.646%, eas) (gnomAD).

ERCC5 p.Asp379=

c.1137C>T · rs56205431 · VCV715964

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.646%, eas)

Conditions

hereditary neoplastic syndrome

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 -8.2	GERP -2.8
Overall
CADD	0.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.646% East Asian · 290/44,870 alleles

Filtering AF 0.585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.561%

Overall 0.0212% 342/1,614,100 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.646%	155
Remaining individualsnot grpmax-eligible	0.0192%	5,209
African / African-American	0.0107%	9,377
European (non-Finnish)	0.00271%	36,876

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.Asp379=
Coding: c.1137C>T
MANE Select: NM_000123
dbSNP: rs56205431
Type: single nucleotide variant
Location: chr13:102862286 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.91 · 10 PDB
Residue 379: the 'spacer region' region; the 'disordered' region

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

Similar variants

ERCC5 p.Glu1090Lys Uncertain significance ★★ ⚠ same condition
ERCC5 p.Glu595Gln Uncertain significance ★★ ⚠ same condition
ERCC5 p.Ala376Val Likely benign ★★ same condition
ERCC5 p.Glu267= Benign/Likely benign ★★ same condition
ERCC5 p.Ala1007Gly Uncertain significance ★ ⚠ same condition
ERCC5 p.Arg1166= Uncertain significance ★ same condition
ERCC5 p.Arg366Gln Uncertain significance ★ ⚠ same condition
ERCC5 p.Glu302Ala Uncertain significance ★ ⚠ 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/ercc5-p-asp379 (accessed [today's date]).

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