Is FKRP p.Val393= (c.1179A>G) pathogenic?

FKRP p.Val393= (c.1179A>G) is classified Benign/Likely benign in FKRP (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-27). Rare (popmax 0.568%, afr); Associated with muscular dystrophy-dystroglycanopathy, type A.

What condition is associated with FKRP p.Val393= (c.1179A>G)?

FKRP p.Val393= (c.1179A>G) is associated with muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Val393= (c.1179A>G) in the general population?

FKRP p.Val393= (c.1179A>G) is rare (popmax 0.568%, afr) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

FKRP p.Val393=

c.1179A>G · rs145894568 · VCV197350

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.568%, afr)

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 4.3	GERP 0.19, phastCons 1
Overall
CADD	9.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.568% African / African-American · 426/75,038 alleles

Filtering AF 0.523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.506%

Overall 0.0309% 498/1,613,082 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.568%	176
Middle Eastern	0.115%	866
Remaining individualsnot grpmax-eligible	0.048%	2,082
Admixed American	0.0468%	2,138
South Asian	0.0022%	45,447
European (non-Finnish)	0.000424%	235,944

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.Val393=
Coding: c.1179A>G
MANE Select: NM_024301
dbSNP: rs145894568
Type: single nucleotide variant
Location: chr19:46756629 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 393: a β-strand

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.Val393Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
FKRP p.Val393Leu 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-val393 (accessed [today's date]).

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