Is CFAP298 p.Leu253Phe (c.757C>T) pathogenic?

CFAP298 p.Leu253Phe (c.757C>T) is classified Uncertain significance in CFAP298 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-19). AlphaMissense: likely benign (0.1644); Absent from gnomAD v4.1.

How common is CFAP298 p.Leu253Phe (c.757C>T) in the general population?

CFAP298 p.Leu253Phe (c.757C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP298 p.Leu253Phe (c.757C>T)?

AlphaMissense predicts likely benign (score 0.1644) — an in-silico prediction, not a clinical call.

CFAP298 p.Leu253Phe

c.757C>T · VCV3684733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1644 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1644	likely benign
REVEL	0.648	pathogenic-leaning
SaProt	LLR -10.82	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 10 kb · p 0.52 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP298
Protein: p.Leu253Phe
Coding: c.757C>T
MANE Select: NM_021254
Type: single nucleotide variant
Location: chr21:32602277 (GRCh38)
Gene constraint: LOEUF 1.267 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54

Full CFAP298 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP298 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same type
CFAP298 p.Gln225Ter Pathogenic ★★ same type
CFAP298 p.Asp141Gly Uncertain significance ★★ ⚠ same type
CFAP298 p.Gln225Arg Uncertain significance ★★ ⚠ same type
CFAP298 p.Gly80Ser Uncertain significance ★★ ⚠ same type
CFAP298 c.308-16C>G Benign ★★ same type
CFAP298 c.375+15A>G Likely benign ★★ same type
CFAP298 c.376-20C>T Benign ★★ 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/cfap298-p-leu253phe (accessed [today's date]).

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