Is XPC p.Asp68Val (c.203A>T) pathogenic?

XPC p.Asp68Val (c.203A>T) is classified Conflicting classifications of pathogenicity in XPC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.0834); Rare (popmax 0.459%, eas); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Asp68Val (c.203A>T)?

XPC p.Asp68Val (c.203A>T) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Asp68Val (c.203A>T) in the general population?

XPC p.Asp68Val (c.203A>T) is rare (popmax 0.459%, eas) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

What do computational predictors say about XPC p.Asp68Val (c.203A>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

XPC p.Asp68Val

c.203A>T · rs56012223 · VCV762370

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.459%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -2.7
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	7.741	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.459% East Asian · 206/44,890 alleles

Filtering AF 0.408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.388%

Overall 0.0132% 213/1,613,988 alleles · rare exomes 196/1,461,668 · genomes 17/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.459%	218
Remaining individualsnot grpmax-eligible	0.0096%	10,414
South Asian	0.0011%	91,078

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: XPC
Protein: p.Asp68Val
Coding: c.203A>T
MANE Select: NM_004628
dbSNP: rs56012223
Type: single nucleotide variant
Location: chr3:14172963 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 68: the 'disordered' region

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

Disease context

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

For Xeroderma pigmentosum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

XPC p.Asp68= Likely benign ★ same residue
XPC c.104-2A>G Likely pathogenic ★★ same condition
XPC c.1872+1G>A Likely pathogenic ★★ same condition
XPC c.1872+1G>C Pathogenic/Likely pathogenic ★★ same condition
XPC c.2033+1G>A Pathogenic/Likely pathogenic ★★ same condition
XPC c.2251-1G>C Pathogenic ★★ same condition
XPC c.2420+2T>C Pathogenic/Likely pathogenic ★★ same condition
XPC c.299+1G>A 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/xpc-p-asp68val (accessed [today's date]).

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