Is CFAP184 p.Ala275Ser (c.823G>T) pathogenic?

CFAP184 p.Ala275Ser (c.823G>T) is classified Uncertain significance in CFAP184 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.0935); Ultra-rare (popmax 0.0404%, nfe).

How common is CFAP184 p.Ala275Ser (c.823G>T) in the general population?

CFAP184 p.Ala275Ser (c.823G>T) is ultra-rare (popmax 0.0404%, nfe) (gnomAD).

What do computational predictors say about CFAP184 p.Ala275Ser (c.823G>T)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

CFAP184 p.Ala275Ser

c.823G>T · rs200732240 · VCV2458230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0404%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -7.64	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 0.37	GERP -2.5, phastCons 0.3
Regional constraint	o/e 1.14	unconstrained · MANE · 1,664 bp · p 0.00013 · regional, not allelic
Overall
CADD	3.579	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 0.0404% European (non-Finnish) · 476/1,179,476 alleles

Filtering AF 0.0373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0362%

Overall 0.0353% 568/1,607,314 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0664%	1,506
European (non-Finnish)grpmax	0.0404%	2,478
Admixed American	0.0403%	2,481
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0289%	3,463
African / African-American	0.00802%	12,470
East Asian	0.00668%	14,960

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP184
Protein: p.Ala275Ser
Coding: c.823G>T
MANE Select: NM_153376
dbSNP: rs200732240
Type: single nucleotide variant
Location: chr4:7042116 (GRCh38)
Structure: AlphaFold pLDDT 69.36 · 1 PDB

Full CFAP184 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP184 p.Ala105Thr Uncertain significance ★ ⚠ same type
CFAP184 p.Ala109Asp Uncertain significance ★ ⚠ same type
CFAP184 p.Ala126Thr Uncertain significance ★ ⚠ same type
CFAP184 p.Ala126Val Uncertain significance ★ ⚠ same type
CFAP184 p.Ala142Val Uncertain significance ★ ⚠ same type
CFAP184 p.Ala160Thr Uncertain significance ★ ⚠ same type
CFAP184 p.Ala374Pro Uncertain significance ★ ⚠ same type
CFAP184 p.Ala469Val 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/cfap184-p-ala275ser (accessed [today's date]).

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