Is ERCC2 c.477+9A>C pathogenic?

ERCC2 c.477+9A>C is classified Benign/Likely benign in ERCC2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 12.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with xeroderma pigmentosum group D.

What condition is associated with ERCC2 c.477+9A>C?

ERCC2 c.477+9A>C is associated with xeroderma pigmentosum group D (ClinVar).

ERCC2 c.477+9A>C

Q: How common is ERCC2 c.477+9A>C in the general population?

ERCC2 c.477+9A>C is common (popmax 12.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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

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

rs1799785 · VCV256022

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 12.6%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

xeroderma pigmentosum group D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.8	GERP -2.7
Non-coding constraint	Z 0.64	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	0.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.6% East Asian · 5,672/44,854 alleles

Filtering AF 12.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.3%

Overall 0.737% 11,880/1,612,340 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	12.6%	8
Admixed American	7.39%	14
Remaining individualsnot grpmax-eligible	0.781%	128
South Asian	0.229%	438
African / African-American	0.133%	750
Middle Eastern	0.116%	865
European (non-Finnish)	0.0808%	1,238
Finnishnot grpmax-eligible	0.0281%	3,556
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592

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: ERCC2
Coding: c.477+9A>C
MANE Select: NM_000400
dbSNP: rs1799785
Type: single nucleotide variant
Location: chr19:45365033 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.74 · 55 PDB

Full ERCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC2 c.1308-2A>G Likely pathogenic ★★ same condition
ERCC2 c.1480-2A>C Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1666-2A>T Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.1759-2A>G Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.183+2T>A Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.361-1G>A Pathogenic/Likely pathogenic ★★ same condition
ERCC2 c.816-2A>G Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Ala717Gly Pathogenic/Likely pathogenic ★★ ⚠ 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/ercc2-c-477-plus-9a-c (accessed [today's date]).

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