Is CFAP58 p.Arg696Cys (c.2086C>T) pathogenic?

CFAP58 p.Arg696Cys (c.2086C>T) is classified Likely benign in CFAP58 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). AlphaMissense: likely benign (0.2005); Low-frequency (popmax 2.22%, mid).

How common is CFAP58 p.Arg696Cys (c.2086C>T) in the general population?

CFAP58 p.Arg696Cys (c.2086C>T) is low-frequency (popmax 2.22%, mid) (gnomAD).

What do computational predictors say about CFAP58 p.Arg696Cys (c.2086C>T)?

AlphaMissense predicts likely benign (score 0.2005) — an in-silico prediction, not a clinical call.

CFAP58 p.Arg696Cys

c.2086C>T · rs41291850 · VCV2498470

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2005 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.22%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2005	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -12.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -3.4, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 101 kb · p 0.33 · regional, not allelic
Overall
CADD	23.0	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 2.22% Middle Eastern · 129/5,818 alleles

Filtering AF 1.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.79%

Overall 0.604% 9,743/1,612,424 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.5%	22
Middle Easterngrpmax	2.22%	45
Ashkenazi Jewishnot grpmax-eligible	1.57%	64
Finnishnot grpmax-eligible	0.682%	147
European (non-Finnish)	0.628%	159
Remaining individualsnot grpmax-eligible	0.614%	163
South Asian	0.546%	183
Admixed American	0.396%	253
African / African-American	0.209%	477

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg696Cys
Coding: c.2086C>T
MANE Select: NM_001008723
dbSNP: rs41291850
Type: single nucleotide variant
Location: chr10:104403775 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 1 PDB
Residue 696: a UniProt-annotated variant site (in spgf49)

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

Similar variants

CFAP58 p.Arg696His 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-arg696cys (accessed [today's date]).

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