Is FKRP p.Ala161= (c.483C>T) pathogenic?

FKRP p.Ala161= (c.483C>T) is classified Conflicting classifications of pathogenicity in FKRP (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0168%, mid); Associated with Cardiovascular phenotype.

How common is FKRP p.Ala161= (c.483C>T) in the general population?

FKRP p.Ala161= (c.483C>T) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

FKRP p.Ala161=

Q: What condition is associated with FKRP p.Ala161= (c.483C>T)?

FKRP p.Ala161= (c.483C>T) is associated with Cardiovascular phenotype, muscular dystrophy-dystroglycanopathy, type A, autosomal recessive limb-girdle muscular dystrophy type 2I (ClinVar).

c.483C>T · rs797045576 · VCV211007

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Conditions

Cardiovascular phenotype

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 0.008	GERP 0.014, phastCons 0.86
Overall
CADD	2.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,950 alleles

Filtering AF 0.00179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.000457% 7/1,531,910 alleles · ultra-rare exomes 3/1,379,690 · genomes 4/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,950
African / African-American	0.00552%	18,118
Remaining individualsnot grpmax-eligible	0.00167%	59,704
South Asian	0.00119%	83,720

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.Ala161=
Coding: c.483C>T
MANE Select: NM_024301
dbSNP: rs797045576
Type: single nucleotide variant
Location: chr19:46755933 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy, type A autosomal recessive limb-girdle muscular dystrophy type 2I

Similar variants

FKRP p.Ala161Thr Uncertain significance ★ ⚠ same residue
FKRP p.Ala161Val 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-ala161 (accessed [today's date]).

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