Is ERCC5 p.Ala98= (c.294G>A) pathogenic?

ERCC5 p.Ala98= (c.294G>A) is classified Conflicting classifications of pathogenicity in ERCC5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-03). Rare (popmax 0.118%, eas); Associated with xeroderma pigmentosum group G.

What condition is associated with ERCC5 p.Ala98= (c.294G>A)?

ERCC5 p.Ala98= (c.294G>A) is associated with xeroderma pigmentosum group G (ClinVar).

How common is ERCC5 p.Ala98= (c.294G>A) in the general population?

ERCC5 p.Ala98= (c.294G>A) is rare (popmax 0.118%, eas) (gnomAD).

ERCC5 p.Ala98=

Q: How is Xeroderma pigmentosum-Cockayne syndrome complex inherited?

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

c.294G>A · rs780506840 · VCV740330

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

Conditions

xeroderma pigmentosum group G

⚠ 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 -2.8	GERP -5
Overall
CADD	0.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% East Asian · 53/44,880 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.00582% 94/1,614,134 alleles · rare exomes 89/1,461,866 · genomes 5/152,268 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.118%	847
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.00305%	32,778
Finnishnot grpmax-eligible	0.00156%	64,008
African / African-American	0.00133%	75,038
South Asian	0.0011%	91,082

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.Ala98=
Coding: c.294G>A
MANE Select: NM_000123
dbSNP: rs780506840
Type: single nucleotide variant
Location: chr13:102853786 (GRCh38)

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

Disease context

xeroderma pigmentosum group G — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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-ala98 (accessed [today's date]).

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