Is CFAP251 p.Pro245Leu (c.734C>T) pathogenic?

CFAP251 p.Pro245Leu (c.734C>T) is classified Uncertain significance in CFAP251 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.1001); Ultra-rare (popmax 0.0228%, afr).

How common is CFAP251 p.Pro245Leu (c.734C>T) in the general population?

CFAP251 p.Pro245Leu (c.734C>T) is ultra-rare (popmax 0.0228%, afr) (gnomAD).

What do computational predictors say about CFAP251 p.Pro245Leu (c.734C>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

CFAP251 p.Pro245Leu

c.734C>T · VCV4001431

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0228%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -2.3
Regional constraint	o/e 0.93	unconstrained · MANE · 82 kb · p 0.0061 · regional, not allelic
Overall
CADD	0.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0228% African / African-American · 17/74,552 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00205% 33/1,608,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0228%	4,385
South Asian	0.00663%	15,077
Remaining individualsnot grpmax-eligible	0.00321%	31,117
East Asian	0.00223%	44,840
European (non-Finnish)	0.000594%	168,281

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.Pro245Leu
Coding: c.734C>T
MANE Select: NM_144668
Type: single nucleotide variant
Location: chr12:121923977 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 245: a UniProt-annotated variant site (in spgf33)

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

Similar variants

CFAP251 p.Arg267Ter Pathogenic ★★ same type
CFAP251 p.Glu111Ter Pathogenic/Likely pathogenic ★★ same type
CFAP251 c.-20-20T>C Benign ★★ same type
CFAP251 p.Arg417Gln Benign ★★ same type
CFAP251 p.Ile970= Likely benign ★★ same type
CFAP251 p.Val307Ile Benign ★★ ⚠ same type
CFAP251 c.-20-2A>C Likely pathogenic ★ same type
CFAP251 p.Gln129Ter Likely pathogenic ★ same type

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-pro245leu (accessed [today's date]).

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