Is CFAP58 p.Leu321Phe (c.961C>T) pathogenic?

CFAP58 p.Leu321Phe (c.961C>T) is classified Uncertain significance in CFAP58 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1049); Absent from gnomAD v4.1.

How common is CFAP58 p.Leu321Phe (c.961C>T) in the general population?

CFAP58 p.Leu321Phe (c.961C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP58 p.Leu321Phe (c.961C>T)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

CFAP58 p.Leu321Phe

c.961C>T · VCV3491379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.94	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 -0.75	GERP -4.3
Regional constraint	o/e 0.97	unconstrained · MANE · 101 kb · p 0.33 · regional, not allelic
Overall
CADD	3.74	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

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: CFAP58
Protein: p.Leu321Phe
Coding: c.961C>T
MANE Select: NM_001008723
Type: single nucleotide variant
Location: chr10:104370925 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 1 PDB

Full CFAP58 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP58 p.Thr783Met Uncertain significance ★★ ⚠ same type
CFAP58 p.Arg698Ter Pathogenic ★ same type
CFAP58 p.Gln454Ter Likely pathogenic ★ same type
CFAP58 c.2039+3A>G Uncertain significance ★ same type
CFAP58 p.Ala102Thr Uncertain significance ★ ⚠ same type
CFAP58 p.Ala177Pro Uncertain significance ★ ⚠ same type
CFAP58 p.Ala311Thr Uncertain significance ★ ⚠ same type
CFAP58 p.Ala311Val Uncertain significance ★ ⚠ 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/cfap58-p-leu321phe (accessed [today's date]).

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