Is CACNA1F p.Ala1908Ser (c.5722G>T) pathogenic?

CACNA1F p.Ala1908Ser (c.5722G>T) is classified Uncertain significance in CACNA1F (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0912); Very rare (popmax 0.00353%, afr); Associated with Inborn genetic diseases.

What condition is associated with CACNA1F p.Ala1908Ser (c.5722G>T)?

CACNA1F p.Ala1908Ser (c.5722G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CACNA1F p.Ala1908Ser (c.5722G>T) in the general population?

CACNA1F p.Ala1908Ser (c.5722G>T) is very rare (popmax 0.00353%, afr) (gnomAD).

What do computational predictors say about CACNA1F p.Ala1908Ser (c.5722G>T)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

CACNA1F p.Ala1908Ser

c.5722G>T · VCV4602985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00353%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP -1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,813 bp · p 0.95 · regional, not allelic
Overall
CADD	22.2	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1919S vs ClinVar A1908S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00353% African / African-American · 2/56,720 alleles

Filtering AF 0.000585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.00181% 2/110,486 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.Ala1908Ser
Coding: c.5722G>T
MANE Select: NM_001256789
Type: single nucleotide variant
Location: chrX:49205316 (GRCh38)
Structure: AlphaFold pLDDT 67.46

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CACNA1F p.Ala1908= Likely benign ★ same residue
CACNA1F p.Gln542Ter Pathogenic ★★ same condition
CACNA1F p.Ala108Gly Uncertain significance ★★ ⚠ same condition
CACNA1F p.Ala1131Ser Uncertain significance ★★ ⚠ same condition
CACNA1F p.Ala1361Thr Uncertain significance ★★ ⚠ same condition
CACNA1F p.Ala1574Ser Uncertain significance ★★ ⚠ same condition
CACNA1F p.Ala1884Gly Uncertain significance ★★ same condition
CACNA1F p.Ala34Asp Uncertain significance ★★ ⚠ same condition

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-ala1908ser (accessed [today's date]).

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