Is FKRP p.Pro316fs (c.947_948del) pathogenic?

FKRP p.Pro316fs (c.947948del) is classified Pathogenic in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). Very rare (popmax 8.64e-05%, nfe); Associated with muscular dystrophy-dystroglycanopathy, type A.

What condition is associated with FKRP p.Pro316fs (c.947_948del)?

FKRP p.Pro316fs (c.947_948del) is associated with muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Pro316fs (c.947_948del) in the general population?

FKRP p.Pro316fs (c.947_948del) is very rare (popmax 8.64e-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.Pro316fs

c.947_948del · rs748798133 · VCV2138311

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.64e-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.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.64	GERP -1.2, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.64e-05% European (non-Finnish) · 1/1,157,332 alleles

Overall 6.38e-05% 1/1,567,114 alleles · very rare exomes 1/1,414,990 · genomes 0/152,124 · joint denominator

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.Pro316fs
Coding: c.947_948del
MANE Select: NM_024301
dbSNP: rs748798133
Type: Deletion
Location: chr19:46756393 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 316: the 'zinc finger loop' region; a UniProt-annotated variant site (in mddgb5 and mddgc5); a UniProt-annotated variant site (in mddgc5); 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.Pro316Arg Pathogenic/Likely pathogenic ★★ same residue
FKRP p.Pro316Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
FKRP p.Pro316= Likely benign ★★ same residue
FKRP p.Pro316Ala Likely pathogenic ★ ⚠ same residue
FKRP p.Pro316Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
FKRP p.Ala150fs Pathogenic ★★ same condition
FKRP p.Ala381fs Pathogenic ★★ same condition
FKRP p.Arg229fs Pathogenic/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-pro316fs (accessed [today's date]).

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