Is XPC p.Asp35Glu (c.105T>A) pathogenic?

XPC p.Asp35Glu (c.105T>A) is classified Likely benign in XPC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.1094); Rare (popmax 0.246%, eas); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Asp35Glu (c.105T>A)?

XPC p.Asp35Glu (c.105T>A) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Asp35Glu (c.105T>A) in the general population?

XPC p.Asp35Glu (c.105T>A) is rare (popmax 0.246%, 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.Asp35Glu (c.105T>A)?

AlphaMissense predicts likely benign (score 0.1094) — an in-silico prediction, not a clinical call.

XPC p.Asp35Glu

c.105T>A · rs202128104 · VCV899822

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1094 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.246%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
AlphaMissense	0.1094	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -4.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.86	acceptor gain · deltas
Pangolin	Δ0.34	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.8	GERP -2.7, phastCons 0.78
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	22.4	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 0.246% East Asian · 109/44,328 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.00713% 112/1,571,444 alleles · rare exomes 104/1,419,204 · genomes 8/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.246%	407
Remaining individualsnot grpmax-eligible	0.00494%	20,253

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.Asp35Glu
Coding: c.105T>A
MANE Select: NM_004628
dbSNP: rs202128104
Type: single nucleotide variant
Location: chr3:14173061 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 35: 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 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
XPC c.413-24A>G 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/xpc-p-asp35glu (accessed [today's date]).

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