Is FKRP p.Pro78Ser (c.232C>T) pathogenic?

FKRP p.Pro78Ser (c.232C>T) is classified Uncertain significance in FKRP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-20). AlphaMissense: likely benign (0.2175); Ultra-rare (popmax 0.0135%, amr); Associated with Cardiovascular phenotype.

How common is FKRP p.Pro78Ser (c.232C>T) in the general population?

FKRP p.Pro78Ser (c.232C>T) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about FKRP p.Pro78Ser (c.232C>T)?

AlphaMissense predicts likely benign (score 0.2175) — an in-silico prediction, not a clinical call.

FKRP p.Pro78Ser

Q: What condition is associated with FKRP p.Pro78Ser (c.232C>T)?

FKRP p.Pro78Ser (c.232C>T) is associated with Cardiovascular phenotype, muscular dystrophy-dystroglycanopathy, type A, autosomal recessive limb-girdle muscular dystrophy type 2I (ClinVar).

c.232C>T · rs747511445 · VCV408720

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2175 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2175	likely benign
REVEL	0.511	indeterminate
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% Admixed American · 8/59,428 alleles

Filtering AF 0.00667% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.000503% 8/1,591,486 alleles · ultra-rare

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.Pro78Ser
Coding: c.232C>T
MANE Select: NM_024301
dbSNP: rs747511445
Type: single nucleotide variant
Location: chr19:46755682 (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.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
FKRP p.Gln105Ter 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-pro78ser (accessed [today's date]).

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