Is FKRP p.Pro247fs (c.740del) pathogenic?

FKRP p.Pro247fs (c.740del) is classified Pathogenic in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-27). Ultra-rare (popmax 0.0184%, mid).

How common is FKRP p.Pro247fs (c.740del) in the general population?

FKRP p.Pro247fs (c.740del) is ultra-rare (popmax 0.0184%, mid) (gnomAD).

FKRP p.Pro247fs

c.740del · rs1568418845 · VCV597598

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, mid)

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 3.4	GERP -0.056, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Middle Eastern · 1/5,436 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000278% 4/1,436,554 alleles · ultra-rare exomes 4/1,285,350 · genomes 0/151,204 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0184%	5,436
South Asian	0.00136%	73,432
European (non-Finnish)	0.000182%	550,373

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.Pro247fs
Coding: c.740del
MANE Select: NM_024301
dbSNP: rs1568418845
Type: Deletion
Location: chr19:46756186 (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

Similar variants

FKRP p.Pro247_Thr250del Likely pathogenic ★ same residue
FKRP p.Pro247Arg Uncertain significance ★ ⚠ same residue
FKRP p.Pro247Gln Conflicting classifications of pathogenicity ★ same residue
FKRP p.Pro247Ser Uncertain significance ★ ⚠ same residue
FKRP p.Pro247Thr Uncertain significance ★ ⚠ same residue
FKRP p.Pro247= Likely benign ★ same residue
FKRP p.Ala150fs Pathogenic ★★ same type
FKRP p.Ala381fs Pathogenic ★★ same type

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-pro247fs (accessed [today's date]).

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