Is FKRP p.Ala198= (c.594T>G) pathogenic?

FKRP p.Ala198= (c.594T>G) is classified Likely benign in FKRP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). Very rare (popmax 0.00862%, amr); Associated with Cardiovascular phenotype.

What condition is associated with FKRP p.Ala198= (c.594T>G)?

FKRP p.Ala198= (c.594T>G) is associated with Cardiovascular phenotype, muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Ala198= (c.594T>G) in the general population?

FKRP p.Ala198= (c.594T>G) is very rare (popmax 0.00862%, amr) (gnomAD).

FKRP p.Ala198=

c.594T>G · rs753158217 · VCV1082819

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00862%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -2
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00862% Admixed American · 5/58,026 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00213%

Overall 0.00038% 6/1,578,358 alleles · very rare exomes 6/1,426,614 · genomes 0/151,744 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00862%	11,605
European (non-Finnish)	8.54e-05%	1,171,005

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: FKRP
Protein: p.Ala198=
Coding: c.594T>G
MANE Select: NM_024301
dbSNP: rs753158217
Type: single nucleotide variant
Location: chr19:46756044 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 198: a β-strand

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy, type A

Similar variants

FKRP p.Ala198Ser Uncertain significance ★ ⚠ same residue
FKRP p.Ala198Thr Uncertain significance ★ ⚠ same residue
FKRP p.Ala157Pro Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Ala321Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
FKRP p.Ala455Asp Pathogenic ★★ same condition
FKRP p.Arg176Ter Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Arg275Cys Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Arg54Gly Likely pathogenic ★★ ⚠ 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/fkrp-p-ala198 (accessed [today's date]).

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