Is ERCC5 p.Arg819= (c.2457G>A) pathogenic?

ERCC5 p.Arg819= (c.2457G>A) is classified Benign/Likely benign in ERCC5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 2.3%, afr); Associated with xeroderma pigmentosum group G.

What condition is associated with ERCC5 p.Arg819= (c.2457G>A)?

ERCC5 p.Arg819= (c.2457G>A) is associated with xeroderma pigmentosum group G (ClinVar).

How common is ERCC5 p.Arg819= (c.2457G>A) in the general population?

ERCC5 p.Arg819= (c.2457G>A) is low-frequency (popmax 2.3%, afr) (gnomAD).

ERCC5 p.Arg819=

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

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

c.2457G>A · rs73573973 · VCV728970

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.3%, 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 0.31	GERP 0.47, phastCons 0.95
Overall
CADD	6.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.3% African / African-American · 1,728/75,066 alleles

Filtering AF 2.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.18%

Overall 0.118% 1,906/1,614,244 alleles · low-frequency exomes 938/1,461,880 · genomes 968/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.3%	43
Remaining individualsnot grpmax-eligible	0.144%	695
Admixed American	0.112%	896
Middle Eastern	0.033%	3,031
East Asian	0.00223%	44,884
South Asian	0.0022%	45,545
European (non-Finnish)	0.00136%	73,752

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.Arg819=
Coding: c.2457G>A
MANE Select: NM_000123
dbSNP: rs73573973
Type: single nucleotide variant
Location: chr13:102866769 (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-arg819 (accessed [today's date]).

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