Is XPC p.Arg579Ter (c.1735C>T) pathogenic?

XPC p.Arg579Ter (c.1735C>T) is classified Pathogenic in XPC (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00446%, eas); Associated with XPC-related disorder.

What condition is associated with XPC p.Arg579Ter (c.1735C>T)?

XPC p.Arg579Ter (c.1735C>T) is associated with XPC-related disorder, xeroderma pigmentosum group C, xeroderma pigmentosum (ClinVar).

How common is XPC p.Arg579Ter (c.1735C>T) in the general population?

XPC p.Arg579Ter (c.1735C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

XPC p.Arg579Ter

c.1735C>T · rs121965088 · VCV259

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

XPC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	42.0	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 0.00446% East Asian · 2/44,864 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000682% 11/1,613,826 alleles · very rare exomes 10/1,461,712 · genomes 1/152,114 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,432
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,978
European (non-Finnish)	0.000509%	196,644

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.Arg579Ter
Coding: c.1735C>T
MANE Select: NM_004628
dbSNP: rs121965088
Type: single nucleotide variant
Location: chr3:14158148 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 579: the 'interaction with rad23b' region

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

Disease context

XPC-related disorder

Also linked: xeroderma pigmentosum group C xeroderma pigmentosum

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-arg579ter (accessed [today's date]).

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