Is CFAP126 p.Arg46Cys (c.136C>T) pathogenic?

CFAP126 p.Arg46Cys (c.136C>T) is classified Uncertain significance in CFAP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1646); Very rare (popmax 0.00666%, afr).

How common is CFAP126 p.Arg46Cys (c.136C>T) in the general population?

CFAP126 p.Arg46Cys (c.136C>T) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about CFAP126 p.Arg46Cys (c.136C>T)?

AlphaMissense predicts likely benign (score 0.1646) — an in-silico prediction, not a clinical call.

CFAP126 p.Arg46Cys

c.136C>T · rs544257853 · VCV2212437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1646	likely benign
REVEL	0.552	indeterminate
SaProt	LLR -12.45	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,900 bp · p 0.0048 · regional, not allelic
Overall
CADD	26.6	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 0.00666% African / African-American · 5/75,042 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00242% 39/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,008
European (non-Finnish)	0.0028%	35,751
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: CFAP126
Protein: p.Arg46Cys
Coding: c.136C>T
MANE Select: NM_001013625
dbSNP: rs544257853
Type: single nucleotide variant
Location: chr1:161366233 (GRCh38)
Gene constraint: LOEUF 1.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.17 · 2 PDB

Full CFAP126 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP126 p.Arg46His Uncertain significance ★ ⚠ same residue
CFAP126 p.Ala90Val Uncertain significance ★ ⚠ same type
CFAP126 p.Arg84Cys Uncertain significance ★ same type
CFAP126 p.Arg84His Uncertain significance ★ ⚠ same type
CFAP126 p.Asp156Asn Uncertain significance ★ ⚠ same type
CFAP126 p.Cys110Ser Uncertain significance ★ ⚠ same type
CFAP126 p.Gln172Glu Uncertain significance ★ ⚠ same type
CFAP126 p.Gly115Arg 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/cfap126-p-arg46cys (accessed [today's date]).

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