Is FKRP p.Arg270= (c.810C>A) pathogenic?

FKRP p.Arg270= (c.810C>A) is classified Likely benign in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-05). Very rare (popmax 8.9e-05%, nfe); Associated with muscular dystrophy-dystroglycanopathy, type A.

What condition is associated with FKRP p.Arg270= (c.810C>A)?

FKRP p.Arg270= (c.810C>A) is associated with muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Arg270= (c.810C>A) in the general population?

FKRP p.Arg270= (c.810C>A) is very rare (popmax 8.9e-05%, nfe) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

FKRP p.Arg270=

c.810C>A · rs754829416 · VCV1532107

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.9e-05%, nfe)

Conditions

muscular dystrophy-dystroglycanopathy, type A

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 0.24	GERP -2.1, phastCons 0.008
Overall
CADD	0.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.9e-05% European (non-Finnish) · 1/1,123,602 alleles

Overall 7.46e-05% 1/1,340,662 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: FKRP
Protein: p.Arg270=
Coding: c.810C>A
MANE Select: NM_024301
dbSNP: rs754829416
Type: single nucleotide variant
Location: chr19:46756260 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 270: an α-helix

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.Arg270His Uncertain significance ★★ ⚠ same residue
FKRP p.Arg270Cys 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-arg270 (accessed [today's date]).

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