Is CFAP161 p.Arg226Trp (c.676C>T) pathogenic?

CFAP161 p.Arg226Trp (c.676C>T) is classified Uncertain significance in CFAP161 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1819); Very rare (popmax 0.00908%, nfe).

How common is CFAP161 p.Arg226Trp (c.676C>T) in the general population?

CFAP161 p.Arg226Trp (c.676C>T) is very rare (popmax 0.00908%, nfe) (gnomAD).

What do computational predictors say about CFAP161 p.Arg226Trp (c.676C>T)?

AlphaMissense predicts likely benign (score 0.1819) — an in-silico prediction, not a clinical call.

CFAP161 p.Arg226Trp

c.676C>T · VCV4226849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00908%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1819	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -12.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.31	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 5.6	phastCons 0.95
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.8 · regional, not allelic
Overall
CADD	26.3	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 0.00908% European (non-Finnish) · 107/1,179,014 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00709%

Overall 0.0072% 116/1,611,296 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00908%	11,019
Remaining individualsnot grpmax-eligible	0.00801%	12,483
Admixed American	0.00335%	29,835
East Asian	0.00223%	44,838
South Asian	0.0011%	90,558

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: CFAP161
Protein: p.Arg226Trp
Coding: c.676C>T
MANE Select: NM_173528
Type: single nucleotide variant
Location: chr15:81147897 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.29 · 2 PDB

Full CFAP161 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP161 p.Arg226Gln Uncertain significance ★ ⚠ same residue
CFAP161 p.Ala115Thr Uncertain significance ★ ⚠ same type
CFAP161 p.Ala295Ser Uncertain significance ★ ⚠ same type
CFAP161 p.Ala2Ser Uncertain significance ★ ⚠ same type
CFAP161 p.Arg203Cys Uncertain significance ★ same type
CFAP161 p.Arg203His Uncertain significance ★ same type
CFAP161 p.Arg87His Uncertain significance ★ ⚠ same type
CFAP161 p.Asn14Lys 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/cfap161-p-arg226trp (accessed [today's date]).

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