Is CFAP184 p.Ala374Pro (c.1120G>C) pathogenic?

CFAP184 p.Ala374Pro (c.1120G>C) is classified Uncertain significance in CFAP184 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.8341); Ultra-rare (popmax 0.0746%, afr).

How common is CFAP184 p.Ala374Pro (c.1120G>C) in the general population?

CFAP184 p.Ala374Pro (c.1120G>C) is ultra-rare (popmax 0.0746%, afr) (gnomAD).

What do computational predictors say about CFAP184 p.Ala374Pro (c.1120G>C)?

AlphaMissense predicts likely pathogenic (score 0.8341) — an in-silico prediction, not a clinical call.

CFAP184 p.Ala374Pro

c.1120G>C · rs143021792 · VCV2348029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8341 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0746%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8341	likely pathogenic · top 6% in CFAP184
REVEL	0.172	moderately benign-leaning
SaProt	LLR -10.47	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1, phastCons 0.78
Regional constraint	o/e 1.14	unconstrained · MANE · 1,664 bp · p 0.00013 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0746% African / African-American · 56/75,048 alleles

Filtering AF 0.0589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.00348% 56/1,610,138 alleles · ultra-rare

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.Ala374Pro
Coding: c.1120G>C
MANE Select: NM_153376
dbSNP: rs143021792
Type: single nucleotide variant
Location: chr4:7041819 (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.Ala275Ser 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-ala374pro (accessed [today's date]).

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