Is FKRP p.Phe56fs (c.162_165dup) pathogenic?

FKRP p.Phe56fs (c.162165dup) is classified Pathogenic/Likely pathogenic in FKRP (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-17). Very rare (popmax 0.00289%, nfe); Associated with FKRP-related disorder.

What condition is associated with FKRP p.Phe56fs (c.162_165dup)?

FKRP p.Phe56fs (c.162_165dup) is associated with FKRP-related disorder, muscular dystrophy-dystroglycanopathy, type A, muscular dystrophy-dystroglycanopathy type B5 (ClinVar).

How common is FKRP p.Phe56fs (c.162_165dup) in the general population?

FKRP p.Phe56fs (c.162_165dup) is very rare (popmax 0.00289%, nfe) (gnomAD).

FKRP p.Phe56fs

c.162_165dup · rs886042506 · VCV282866

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00289%, nfe)

Conditions

FKRP-related disorder

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 2.2	GERP 0.28, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00289% European (non-Finnish) · 34/1,177,352 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00237% 38/1,604,934 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00322%	31,068
European (non-Finnish)grpmax	0.00289%	34,628
African / African-American	0.00267%	37,386

Remaining individuals 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.Phe56fs
Coding: c.162_165dup
MANE Select: NM_024301
dbSNP: rs886042506
Type: Duplication
Location: chr19:46755610 (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

FKRP-related disorder

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 autosomal recessive limb-girdle muscular dystrophy

Similar variants

FKRP p.Ala397fs Pathogenic ★★ same condition
FKRP p.Arg404fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Arg48fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Asn172fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Cys191fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Glu55fs Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Glu334_Arg339dup Uncertain significance ★★ same condition
FKRP p.Leu93_Pro94dup Uncertain significance ★★ 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-phe56fs (accessed [today's date]).

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