Is FKRP p.Arg190Pro (c.569G>C) pathogenic?

FKRP p.Arg190Pro (c.569G>C) is classified Uncertain significance in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.1356); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with FKRP p.Arg190Pro (c.569G>C)?

FKRP p.Arg190Pro (c.569G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is FKRP p.Arg190Pro (c.569G>C) in the general population?

FKRP p.Arg190Pro (c.569G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FKRP p.Arg190Pro (c.569G>C)?

AlphaMissense predicts likely benign (score 0.1356) — an in-silico prediction, not a clinical call.

FKRP p.Arg190Pro

c.569G>C · rs917645867 · VCV2256139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1356 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1356	likely benign
REVEL	0.565	indeterminate
SaProt	LLR -12.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.99, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	16.48	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FKRP
Protein: p.Arg190Pro
Coding: c.569G>C
MANE Select: NM_024301
dbSNP: rs917645867
Type: single nucleotide variant
Location: chr19:46756019 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 190: a disulfide bond; 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

Similar variants

FKRP p.Arg190His Uncertain significance ★★ ⚠ same residue
FKRP p.Arg190Cys Uncertain significance ★ same residue
FKRP p.Gln460Ter Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Gln77Ter Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Pro462Ser Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Pro89Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
FKRP c.-2C>A Uncertain significance ★★ same condition
FKRP p.Ala102Glu 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/fkrp-p-arg190pro (accessed [today's date]).

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