Is XPC p.Arg718fs (c.2153del) pathogenic?

XPC p.Arg718fs (c.2153del) is classified Likely pathogenic in XPC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-22). No gnomAD frequency available for this variant; Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Arg718fs (c.2153del)?

XPC p.Arg718fs (c.2153del) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Arg718fs (c.2153del) in the general population?

XPC p.Arg718fs (c.2153del) is no gnomAD frequency available for this variant (gnomAD).

How is Xeroderma pigmentosum inherited?

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

XPC p.Arg718fs

c.2153del · rs2470227583 · VCV3240749

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 12 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.24	GERP -3.1, phastCons 0.96

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: XPC
Protein: p.Arg718fs
Coding: c.2153del
MANE Select: NM_004628
dbSNP: rs2470227583
Type: Deletion
Location: chr3:14148911 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 718: the 'interaction with rad23b' region; the 'minimal sensor domain involved in damage recognition' region; the 'dna-binding; preference for heteroduplex dna' 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.Arg718Ter Pathogenic ★★ same residue
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

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-arg718fs (accessed [today's date]).

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