Is CFAP161 p.Cys93Ser (c.278G>C) pathogenic?

CFAP161 p.Cys93Ser (c.278G>C) is classified Uncertain significance in CFAP161 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.198); Ultra-rare (popmax 0.0466%, afr).

How common is CFAP161 p.Cys93Ser (c.278G>C) in the general population?

CFAP161 p.Cys93Ser (c.278G>C) is ultra-rare (popmax 0.0466%, afr) (gnomAD).

What do computational predictors say about CFAP161 p.Cys93Ser (c.278G>C)?

AlphaMissense predicts likely benign (score 0.198) — an in-silico prediction, not a clinical call.

CFAP161 p.Cys93Ser

c.278G>C · VCV4001397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0466%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.198	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -4.50	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 8.8	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.8 · regional, not allelic
Overall
CADD	21.0	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 0.0466% African / African-American · 35/75,046 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.0026% 42/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0466%	2,144
Admixed American	0.00666%	15,004
Remaining individualsnot grpmax-eligible	0.0032%	31,256
South Asian	0.0011%	91,070

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.Cys93Ser
Coding: c.278G>C
MANE Select: NM_173528
Type: single nucleotide variant
Location: chr15:81136634 (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-cys93ser (accessed [today's date]).

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