Is FKRP p.Ala321fs (c.960_970del) pathogenic?

FKRP p.Ala321fs (c.960970del) is classified Pathogenic in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-03). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2I.

What condition is associated with FKRP p.Ala321fs (c.960_970del)?

FKRP p.Ala321fs (c.960_970del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2I (ClinVar).

How common is FKRP p.Ala321fs (c.960_970del) in the general population?

FKRP p.Ala321fs (c.960_970del) is absent from gnomAD (gnomAD).

How is FKRP-related limb-girdle muscular dystrophy R9 inherited?

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

FKRP p.Ala321fs

c.960_970del · rs1599937963 · VCV694028

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2I

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 7.6	GERP 1.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FKRP
Protein: p.Ala321fs
Coding: c.960_970del
MANE Select: NM_024301
dbSNP: rs1599937963
Type: Deletion
Location: chr19:46756407 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 321: an α-helix

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For FKRP-related limb-girdle muscular dystrophy R9 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

FKRP p.Ala321Glu Pathogenic/Likely pathogenic ★★ ⚠ same residue
FKRP p.Arg229fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Arg423fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Gly219fs Pathogenic ★★ same condition
FKRP p.Lys472fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Ser211fs Likely pathogenic ★★ same condition
FKRP p.Ser69del Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Thr226fs 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-ala321fs (accessed [today's date]).

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