Is CFAP251 p.Thr806Ser (c.2417C>G) pathogenic?

CFAP251 p.Thr806Ser (c.2417C>G) is classified Uncertain significance in CFAP251 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1296); Very rare (popmax 0.000508%, nfe).

How common is CFAP251 p.Thr806Ser (c.2417C>G) in the general population?

CFAP251 p.Thr806Ser (c.2417C>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CFAP251 p.Thr806Ser (c.2417C>G)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

CFAP251 p.Thr806Ser

c.2417C>G · VCV4226910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -4.56	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 1.4	GERP 0.38, phastCons 0.82
Regional constraint	o/e 0.93	unconstrained · MANE · 82 kb · p 0.0061 · regional, not allelic
Overall
CADD	13.39	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 0.000508% European (non-Finnish) · 6/1,180,044 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,914 alleles · very rare

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.Thr806Ser
Coding: c.2417C>G
MANE Select: NM_144668
Type: single nucleotide variant
Location: chr12:121962087 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 806: 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.Thr806Asn Uncertain significance ★ ⚠ same residue
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

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-thr806ser (accessed [today's date]).

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