Is XPC p.Ala902fs (c.2703del) pathogenic?

XPC p.Ala902fs (c.2703del) is classified Uncertain significance in XPC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-02-28). Very rare (popmax 0.00223%, eas); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Ala902fs (c.2703del)?

XPC p.Ala902fs (c.2703del) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Ala902fs (c.2703del) in the general population?

XPC p.Ala902fs (c.2703del) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

XPC p.Ala902fs

c.2703del · rs1280251289 · VCV556883

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (16 of 16) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,844 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,612,834 alleles · very rare exomes 9/1,461,162 · genomes 1/151,672 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,844
European (non-Finnish)	0.000763%	131,066

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.Ala902fs
Coding: c.2703del
MANE Select: NM_004628
dbSNP: rs1280251289
Type: Deletion
Location: chr3:14146061 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 902: the 'disordered' region; the 'interaction with ercc2 and gtf2h1' 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.Ala674fs Pathogenic/Likely pathogenic ★★ same condition
XPC p.Arg314fs Pathogenic ★★ same condition
XPC p.Arg423fs Pathogenic/Likely pathogenic ★★ same condition
XPC p.Asp121fs Pathogenic/Likely pathogenic ★★ same condition
XPC p.Gln368fs Pathogenic ★★ same condition
XPC p.Gln742fs Pathogenic ★★ same condition
XPC p.Glu141fs Pathogenic ★★ same condition
XPC p.Glu726fs 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-ala902fs (accessed [today's date]).

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