Is CFAP58 p.Arg736Ser (c.2206C>A) pathogenic?

CFAP58 p.Arg736Ser (c.2206C>A) is classified Uncertain significance in CFAP58 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely pathogenic (0.5843); Absent from gnomAD v4.1.

How common is CFAP58 p.Arg736Ser (c.2206C>A) in the general population?

CFAP58 p.Arg736Ser (c.2206C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP58 p.Arg736Ser (c.2206C>A)?

AlphaMissense predicts likely pathogenic (score 0.5843) — an in-silico prediction, not a clinical call.

CFAP58 p.Arg736Ser

c.2206C>A · rs761602798 · VCV2258066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5843 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5843	likely pathogenic
REVEL	0.422	indeterminate
SaProt	LLR -14.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 101 kb · p 0.33 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Arg736Ser
Coding: c.2206C>A
MANE Select: NM_001008723
dbSNP: rs761602798
Type: single nucleotide variant
Location: chr10:104406743 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 1 PDB
Residue 736: a UniProt-annotated variant site (in spgf49); a UniProt-annotated variant site (in spgf49; results in loss of mutant protein; results in axonemal abnormalities)

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

Similar variants

CFAP58 p.Arg736His Uncertain significance ★ ⚠ same residue
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

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-arg736ser (accessed [today's date]).

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