Is ERCC5 p.Ile807= (c.2421C>T) pathogenic?

ERCC5 p.Ile807= (c.2421C>T) is classified Conflicting classifications of pathogenicity in ERCC5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0379%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with ERCC5 p.Ile807= (c.2421C>T)?

ERCC5 p.Ile807= (c.2421C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ERCC5 p.Ile807= (c.2421C>T) in the general population?

ERCC5 p.Ile807= (c.2421C>T) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

ERCC5 p.Ile807=

c.2421C>T · rs199648606 · VCV730096

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, 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 3.9	GERP 2.3, phastCons 1
Overall
CADD	11.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,902 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00235% 38/1,614,158 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,641
Remaining individualsnot grpmax-eligible	0.0208%	4,807
African / African-American	0.00934%	10,707
Admixed American	0.00167%	60,012

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.Ile807=
Coding: c.2421C>T
MANE Select: NM_000123
dbSNP: rs199648606
Type: single nucleotide variant
Location: chr13:102866733 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.91 · 10 PDB
Residue 807: the 'i-domain' 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.Asp379= 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

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-ile807 (accessed [today's date]).

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