Is CFAP58 p.Ala396Val (c.1187C>T) pathogenic?

CFAP58 p.Ala396Val (c.1187C>T) is classified Uncertain significance in CFAP58 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely benign (0.179); Ultra-rare (popmax 0.0164%, mid).

How common is CFAP58 p.Ala396Val (c.1187C>T) in the general population?

CFAP58 p.Ala396Val (c.1187C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CFAP58 p.Ala396Val (c.1187C>T)?

AlphaMissense predicts likely benign (score 0.179) — an in-silico prediction, not a clinical call.

CFAP58 p.Ala396Val

c.1187C>T · rs568288972 · VCV2372381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.179 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.179	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -8.28	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 3.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 101 kb · p 0.33 · regional, not allelic
Overall
CADD	23.9	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00285% 46/1,613,362 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0064%	15,616
East Asian	0.00446%	22,437
South Asian	0.0044%	22,746
European (non-Finnish)	0.00288%	34,698
African / African-American	0.00134%	74,858

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: CFAP58
Protein: p.Ala396Val
Coding: c.1187C>T
MANE Select: NM_001008723
dbSNP: rs568288972
Type: single nucleotide variant
Location: chr10:104380042 (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-ala396val (accessed [today's date]).

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