Is CFAP251 p.Arg267Ter (c.799C>T) pathogenic?

CFAP251 p.Arg267Ter (c.799C>T) is classified Pathogenic in CFAP251 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-30). Very rare (popmax 0.00456%, eas); Associated with CFAP251-related disorder.

What condition is associated with CFAP251 p.Arg267Ter (c.799C>T)?

CFAP251 p.Arg267Ter (c.799C>T) is associated with CFAP251-related disorder, spermatogenic failure 33 (ClinVar).

How common is CFAP251 p.Arg267Ter (c.799C>T) in the general population?

CFAP251 p.Arg267Ter (c.799C>T) is very rare (popmax 0.00456%, eas) (gnomAD).

CFAP251 p.Arg267Ter

c.799C>T · rs745817765 · VCV2636927

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00456%, eas)

Conditions

CFAP251-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 4 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.5, phastCons 0.14
Overall
CADD	38.0	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 0.00456% East Asian · 2/43,876 alleles

Filtering AF 0.000756% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000283%

Overall 0.000624% 10/1,602,036 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00456%	21,938
Remaining individualsnot grpmax-eligible	0.00161%	61,942
European (non-Finnish)	0.000596%	167,841

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: CFAP251
Protein: p.Arg267Ter
Coding: c.799C>T
MANE Select: NM_144668
dbSNP: rs745817765
Type: single nucleotide variant
Location: chr12:121931797 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 267: a UniProt-annotated variant site (in spgf33)

Full CFAP251 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CFAP251-related disorder

Also linked: spermatogenic failure 33

Similar variants

CFAP251 p.Glu111Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP251 c.-20-2A>C Likely pathogenic ★ same condition
CFAP251 p.Gln129Ter Likely pathogenic ★ same condition
CFAP251 c.1191+4A>G Uncertain significance ★ same condition
CFAP251 c.2771+11G>C Uncertain significance ★ same condition
CFAP251 c.2492+10C>G Likely benign same condition
CFAP251 p.Asn286= Benign same condition
CFAP251 p.Asp511= Likely benign 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/cfap251-p-arg267ter (accessed [today's date]).

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