Is ERCC5 p.Asp730= (c.2190T>C) pathogenic?

ERCC5 p.Asp730= (c.2190T>C) is classified Conflicting classifications of pathogenicity in ERCC5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-09-01). Ultra-rare (popmax 0.064%, afr); Associated with xeroderma pigmentosum group G.

What condition is associated with ERCC5 p.Asp730= (c.2190T>C)?

ERCC5 p.Asp730= (c.2190T>C) is associated with xeroderma pigmentosum group G (ClinVar).

How common is ERCC5 p.Asp730= (c.2190T>C) in the general population?

ERCC5 p.Asp730= (c.2190T>C) is ultra-rare (popmax 0.064%, afr) (gnomAD).

ERCC5 p.Asp730=

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

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

c.2190T>C · rs148103512 · VCV310928

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.064%, afr)

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 -0.22, phastCons 1
Overall
CADD	7.993	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.064% African / African-American · 48/75,038 alleles

Filtering AF 0.0495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.00347% 56/1,613,948 alleles · ultra-rare exomes 28/1,461,640 · genomes 28/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.064%	1,563
Admixed American	0.00666%	15,007
Remaining individualsnot grpmax-eligible	0.0032%	31,249
East Asian	0.00223%	44,882
European (non-Finnish)	8.48e-05%	1,179,830

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.Asp730=
Coding: c.2190T>C
MANE Select: NM_000123
dbSNP: rs148103512
Type: single nucleotide variant
Location: chr13:102865902 (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-asp730 (accessed [today's date]).

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