Is FKRP p.Ala83= (c.249C>T) pathogenic?

FKRP p.Ala83= (c.249C>T) is classified Benign/Likely benign in FKRP (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.09%, mid); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1.

What condition is associated with FKRP p.Ala83= (c.249C>T)?

FKRP p.Ala83= (c.249C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1, muscular dystrophy-dystroglycanopathy, type A, muscular dystrophy-dystroglycanopathy type B5 (ClinVar).

How common is FKRP p.Ala83= (c.249C>T) in the general population?

FKRP p.Ala83= (c.249C>T) is low-frequency (popmax 2.09%, mid) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

FKRP p.Ala83=

c.249C>T · rs149030303 · VCV96107

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, mid)

Conditions

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

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 -11	GERP -2.8
Overall
CADD	1.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% Middle Eastern · 126/6,028 alleles

Filtering AF 1.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.69%

Overall 1.29% 20,432/1,582,434 alleles · low-frequency exomes 19,023/1,430,104 · genomes 1,409/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.09%	48
South Asian	1.79%	56
European (non-Finnish)	1.43%	70
Finnishnot grpmax-eligible	1.4%	71
Ashkenazi Jewishnot grpmax-eligible	1.15%	87
Remaining individualsnot grpmax-eligible	1.07%	94
Admixed American	0.275%	363
African / African-American	0.239%	418
Amishnot grpmax-eligible	0.219%	456
East Asian	0.0023%	43,526

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.Ala83=
Coding: c.249C>T
MANE Select: NM_024301
dbSNP: rs149030303
Type: single nucleotide variant
Location: chr19:46755699 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 83: a β-strand

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

Disease context

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy, type A muscular dystrophy-dystroglycanopathy type B5 autosomal recessive limb-girdle muscular dystrophy type 2I muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5

For Walker-Warburg syndrome (Orphanet):

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

Similar variants

FKRP p.Ala83_Asp84insAla 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
FKRP p.Asn463Asp 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-ala83 (accessed [today's date]).

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