Is CFAP184 p.Arg509Pro (c.1526G>C) pathogenic?

CFAP184 p.Arg509Pro (c.1526G>C) is classified Uncertain significance in CFAP184 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.8917); Very rare (popmax 0.000137%).

How common is CFAP184 p.Arg509Pro (c.1526G>C) in the general population?

CFAP184 p.Arg509Pro (c.1526G>C) is very rare (popmax 0.000137%) (gnomAD).

What do computational predictors say about CFAP184 p.Arg509Pro (c.1526G>C)?

AlphaMissense predicts likely pathogenic (score 0.8917) — an in-silico prediction, not a clinical call.

CFAP184 p.Arg509Pro

c.1526G>C · VCV4226867

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8917	likely pathogenic · top 4% in CFAP184
REVEL	0.18	moderately benign-leaning
SaProt	LLR -11.00	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 -0.24	GERP -1.7
Regional constraint	o/e 1.14	unconstrained · MANE · 1,664 bp · p 0.00013 · regional, not allelic
Overall
CADD	19.33	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 0.000137%

Overall 0.000137% 2/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,038

Remaining individuals 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.Arg509Pro
Coding: c.1526G>C
MANE Select: NM_153376
Type: single nucleotide variant
Location: chr4:7041413 (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.Arg509Gly Uncertain significance ★ ⚠ same residue
CFAP184 p.Arg509Trp Uncertain significance ★ ⚠ same residue
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

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-arg509pro (accessed [today's date]).

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