Is FKRP p.Arg134Pro (c.401G>C) pathogenic?

FKRP p.Arg134Pro (c.401G>C) is classified Uncertain significance in FKRP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-22). AlphaMissense: likely pathogenic (0.639); Absent from gnomAD v4.1.

How common is FKRP p.Arg134Pro (c.401G>C) in the general population?

FKRP p.Arg134Pro (c.401G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FKRP p.Arg134Pro (c.401G>C)?

AlphaMissense predicts likely pathogenic (score 0.639) — an in-silico prediction, not a clinical call.

FKRP p.Arg134Pro

c.401G>C · rs886042579 · VCV283231

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.639 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.639	likely pathogenic
REVEL	0.555	indeterminate
SaProt	LLR -12.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Arg134Pro
Coding: c.401G>C
MANE Select: NM_024301
dbSNP: rs886042579
Type: single nucleotide variant
Location: chr19:46755851 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 134: a UniProt-annotated variant site (in mddgc5)

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

Similar variants

FKRP p.Arg134Trp Uncertain significance ★ ⚠ same residue
FKRP p.Arg134_Ala135insTer Likely pathogenic same residue
FKRP p.Ala157Pro Pathogenic/Likely pathogenic ★★ same type
FKRP p.Ala321Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
FKRP p.Ala455Asp Pathogenic ★★ same type
FKRP p.Arg176Ter Pathogenic/Likely pathogenic ★★ same type
FKRP p.Arg275Cys Pathogenic/Likely pathogenic ★★ same type
FKRP p.Arg54Gly Likely 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/fkrp-p-arg134pro (accessed [today's date]).

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