Is FKRP p.Arg41Ser (c.121C>A) pathogenic?

FKRP p.Arg41Ser (c.121C>A) is classified Uncertain significance in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1512); Absent from gnomAD v4.1; Associated with muscular dystrophy-dystroglycanopathy, type A.

What condition is associated with FKRP p.Arg41Ser (c.121C>A)?

FKRP p.Arg41Ser (c.121C>A) is associated with muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Arg41Ser (c.121C>A) in the general population?

FKRP p.Arg41Ser (c.121C>A) is absent from gnomAD v4.1 (gnomAD).

How is Walker-Warburg syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FKRP p.Arg41Ser (c.121C>A)?

AlphaMissense predicts likely benign (score 0.1512) — an in-silico prediction, not a clinical call.

FKRP p.Arg41Ser

c.121C>A · rs2122609166 · VCV1478958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1512 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

muscular dystrophy-dystroglycanopathy, type A

Computational evidence

Protein change
AlphaMissense	0.1512	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.32, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	14.75	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.

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.Arg41Ser
Coding: c.121C>A
MANE Select: NM_024301
dbSNP: rs2122609166
Type: single nucleotide variant
Location: chr19:46755571 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB

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

Disease context

muscular dystrophy-dystroglycanopathy, type A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

FKRP p.Arg41His Uncertain significance ★★ ⚠ same residue
FKRP p.Arg41Leu 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-arg41ser (accessed [today's date]).

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