Is CFAP58 p.Gln86Arg (c.257A>G) pathogenic?

CFAP58 p.Gln86Arg (c.257A>G) is classified Uncertain significance in CFAP58 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1986); Very rare (popmax 0.00801%, afr).

How common is CFAP58 p.Gln86Arg (c.257A>G) in the general population?

CFAP58 p.Gln86Arg (c.257A>G) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CFAP58 p.Gln86Arg (c.257A>G)?

AlphaMissense predicts likely benign (score 0.1986) — an in-silico prediction, not a clinical call.

CFAP58 p.Gln86Arg

c.257A>G · VCV4001580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1986	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -12.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 101 kb · p 0.33 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.00801% African / African-American · 6/74,908 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000434% 7/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
Admixed American	0.00167%	59,982

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.Gln86Arg
Coding: c.257A>G
MANE Select: NM_001008723
Type: single nucleotide variant
Location: chr10:104358588 (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-gln86arg (accessed [today's date]).

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