Is FKRP p.Phe473= (c.1419C>T) pathogenic?

FKRP p.Phe473= (c.1419C>T) is classified Likely benign in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). Very rare (popmax 0.00102%, nfe); Associated with muscular dystrophy-dystroglycanopathy, type A.

What condition is associated with FKRP p.Phe473= (c.1419C>T)?

FKRP p.Phe473= (c.1419C>T) is associated with muscular dystrophy-dystroglycanopathy, type A (ClinVar).

How common is FKRP p.Phe473= (c.1419C>T) in the general population?

FKRP p.Phe473= (c.1419C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

FKRP p.Phe473=

c.1419C>T · rs868310782 · VCV1154255

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

muscular dystrophy-dystroglycanopathy, type A

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 -2.5	GERP -1.5
Overall
CADD	7.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,136 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000891% 13/1,458,866 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,394
European (non-Finnish)grpmax	0.00102%	98,262

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.Phe473=
Coding: c.1419C>T
MANE Select: NM_024301
dbSNP: rs868310782
Type: single nucleotide variant
Location: chr19:46756869 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 473: an α-helix

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

Disease context

muscular dystrophy-dystroglycanopathy, type A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Walker-Warburg syndrome (Orphanet):

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

Similar variants

FKRP p.Phe473Cys Conflicting classifications of pathogenicity ★ ⚠ 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-phe473 (accessed [today's date]).

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