Is CFAP161 p.Ser176Phe (c.527C>T) pathogenic?

CFAP161 p.Ser176Phe (c.527C>T) is classified Uncertain significance in CFAP161 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.801); Very rare (popmax 0.00475%, nfe).

How common is CFAP161 p.Ser176Phe (c.527C>T) in the general population?

CFAP161 p.Ser176Phe (c.527C>T) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about CFAP161 p.Ser176Phe (c.527C>T)?

AlphaMissense predicts likely pathogenic (score 0.801) — an in-silico prediction, not a clinical call.

CFAP161 p.Ser176Phe

c.527C>T · VCV4226850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.801	likely pathogenic · top 9% in CFAP161
REVEL	0.394	indeterminate
SaProt	LLR -13.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.8 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00475% European (non-Finnish) · 56/1,180,020 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00397% 58/1,461,854 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00475%	21,072
Remaining individualsnot grpmax-eligible	0.0016%	62,508
African / African-American	0.00133%	75,012

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.Ser176Phe
Coding: c.527C>T
MANE Select: NM_173528
Type: single nucleotide variant
Location: chr15:81143711 (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-ser176phe (accessed [today's date]).

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