Is CFAP251 p.Pro1099= (c.3297C>T) pathogenic?

CFAP251 p.Pro1099= (c.3297C>T) is classified Likely benign in CFAP251 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Rare (popmax 0.215%, mid); Associated with CFAP251-related disorder.

What condition is associated with CFAP251 p.Pro1099= (c.3297C>T)?

CFAP251 p.Pro1099= (c.3297C>T) is associated with CFAP251-related disorder (ClinVar).

How common is CFAP251 p.Pro1099= (c.3297C>T) in the general population?

CFAP251 p.Pro1099= (c.3297C>T) is rare (popmax 0.215%, mid) (gnomAD).

CFAP251 p.Pro1099=

c.3297C>T · VCV3350914

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.215%, mid)

Conditions

CFAP251-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.4
Overall
CADD	0.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% Middle Eastern · 13/6,060 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00167% 27/1,614,022 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.215%	466
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-American	0.00267%	37,495
East Asian	0.00223%	44,870
Admixed American	0.00167%	60,000
South Asian	0.0011%	91,080
European (non-Finnish)	0.000593%	168,572

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.Pro1099=
Coding: c.3297C>T
MANE Select: NM_144668
Type: single nucleotide variant
Location: chr12:122001558 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 1099: 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

Similar variants

CFAP251 p.Pro1099Thr Uncertain significance ★ ⚠ same residue
CFAP251 p.Arg267Ter Pathogenic ★★ same condition
CFAP251 c.2492+10C>G Likely benign same condition
CFAP251 p.Asn286= Benign same condition
CFAP251 p.Asp511= Likely benign same condition
CFAP251 p.Glu207= Likely benign same condition
CFAP251 p.Gly649= Likely benign same condition
CFAP251 p.His356= 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-pro1099 (accessed [today's date]).

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