Is CFAP161 p.Pro285Arg (c.854C>G) pathogenic?

CFAP161 p.Pro285Arg (c.854C>G) is classified Uncertain significance in CFAP161 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00246%, nfe).

How common is CFAP161 p.Pro285Arg (c.854C>G) in the general population?

CFAP161 p.Pro285Arg (c.854C>G) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about CFAP161 p.Pro285Arg (c.854C>G)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

CFAP161 p.Pro285Arg

c.854C>G · VCV4652750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -7.06	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 -3.8
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.8 · regional, not allelic
Overall
CADD	2.591	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 0.00246% European (non-Finnish) · 29/1,180,034 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00186% 30/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,691
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: CFAP161
Protein: p.Pro285Arg
Coding: c.854C>G
MANE Select: NM_173528
Type: single nucleotide variant
Location: chr15:81148481 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.29 · 2 PDB
Residue 285: the 'disordered' region

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-pro285arg (accessed [today's date]).

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