Is CACNA1F p.Arg513Pro (c.1538G>C) pathogenic?

CACNA1F p.Arg513Pro (c.1538G>C) is classified Uncertain significance in CACNA1F (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: ambiguous (0.5476); Very rare (popmax 0.00102%, nfe).

How common is CACNA1F p.Arg513Pro (c.1538G>C) in the general population?

CACNA1F p.Arg513Pro (c.1538G>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about CACNA1F p.Arg513Pro (c.1538G>C)?

AlphaMissense predicts ambiguous (score 0.5476) — an in-silico prediction, not a clinical call.

CACNA1F p.Arg513Pro

c.1538G>C · rs782288797 · VCV3002466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5476 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5476	ambiguous
REVEL	0.456	indeterminate
SaProt	LLR -14.50	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.7
Regional constraint	o/e 0.84	unconstrained · MANE · 21 kb · p 1.1e-07 · regional, not allelic
Overall
CADD	16.06	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R524P vs ClinVar R513P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 9/882,635 alleles

Filtering AF 0.00048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000347%

Overall 0.000838% 9/1,073,671 alleles · very 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: CACNA1F
Protein: p.Arg513Pro
Coding: c.1538G>C
MANE Select: NM_001256789
dbSNP: rs782288797
Type: single nucleotide variant
Location: chrX:49226022 (GRCh38)
Structure: AlphaFold pLDDT 67.46

Full CACNA1F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNA1F p.Arg513Gln Uncertain significance ★★ ⚠ same residue
CACNA1F p.Arg513Trp Uncertain significance ★★ ⚠ same residue
CACNA1F c.1118+1G>C Pathogenic ★★ same type
CACNA1F c.2086-1G>C Pathogenic/Likely pathogenic ★★ same type
CACNA1F c.2086-2A>G Pathogenic/Likely pathogenic ★★ same type
CACNA1F c.2543+1G>A Pathogenic ★★ same type
CACNA1F c.2674-2A>G Likely pathogenic ★★ same type
CACNA1F c.2928+1G>A Pathogenic ★★ 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/cacna1f-p-arg513pro (accessed [today's date]).

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