Is CFAP161 p.Pro75Leu (c.224C>T) pathogenic?

CFAP161 p.Pro75Leu (c.224C>T) is classified Uncertain significance in CFAP161 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.0982); Very rare (popmax 0.00167%, amr).

How common is CFAP161 p.Pro75Leu (c.224C>T) in the general population?

CFAP161 p.Pro75Leu (c.224C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CFAP161 p.Pro75Leu (c.224C>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

CFAP161 p.Pro75Leu

c.224C>T · VCV4226853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	phastCons 0.048
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.8 · regional, not allelic
Overall
CADD	19.73	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00167% Admixed American · 1/60,018 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
European (non-Finnish)	0.000593%	168,576

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.Pro75Leu
Coding: c.224C>T
MANE Select: NM_173528
Type: single nucleotide variant
Location: chr15:81136580 (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.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.Arg226Gln Uncertain significance ★ ⚠ same type
CFAP161 p.Arg226Trp Uncertain significance ★ ⚠ same type
CFAP161 p.Arg87His 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-pro75leu (accessed [today's date]).

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