Is FKRP p.Ala9Val (c.26C>T) pathogenic?

FKRP p.Ala9Val (c.26C>T) is classified Uncertain significance in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). AlphaMissense: likely benign (0.0956); Very rare (popmax 0.0011%, sas); Associated with muscular dystrophy-dystroglycanopathy, type A.

What condition is associated with FKRP p.Ala9Val (c.26C>T)?

FKRP p.Ala9Val (c.26C>T) is associated with muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Ala9Val (c.26C>T) in the general population?

FKRP p.Ala9Val (c.26C>T) is very rare (popmax 0.0011%, sas) (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.Ala9Val (c.26C>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

FKRP p.Ala9Val

c.26C>T · rs772755355 · VCV2145390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

muscular dystrophy-dystroglycanopathy, type A

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.078	GERP -0.001, phastCons 0.002
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	8.409	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

Grpmax group 0.0011% South Asian · 1/90,810 alleles

Overall 0.000249% 4/1,608,838 alleles · very rare exomes 4/1,456,486 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00166%	60,196
Remaining individualsnot grpmax-eligible	0.0016%	62,308
South Asiangrpmax	0.0011%	90,810
European (non-Finnish)	8.48e-05%	1,179,294

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala9Val
Coding: c.26C>T
MANE Select: NM_024301
dbSNP: rs772755355
Type: single nucleotide variant
Location: chr19:46755476 (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.Ala9= Likely benign ★ same residue
STRN4 p.Ala9Glu 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-ala9val (accessed [today's date]).

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