Is FKRP p.His412= (c.1236C>T) pathogenic?

FKRP p.His412= (c.1236C>T) is classified Conflicting classifications of pathogenicity in FKRP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). Rare (popmax 0.221%, eas); Associated with Cardiovascular phenotype.

How common is FKRP p.His412= (c.1236C>T) in the general population?

FKRP p.His412= (c.1236C>T) is rare (popmax 0.221%, eas) (gnomAD).

FKRP p.His412=

Q: What condition is associated with FKRP p.His412= (c.1236C>T)?

FKRP p.His412= (c.1236C>T) is associated with Cardiovascular phenotype, muscular dystrophy-dystroglycanopathy, type A, autosomal recessive limb-girdle muscular dystrophy type 2I (ClinVar).

c.1236C>T · rs201076863 · VCV596929

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.221%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.8	GERP 0.17, phastCons 1
Overall
CADD	5.174	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.221% East Asian · 99/44,866 alleles

Filtering AF 0.185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.00663% 107/1,613,274 alleles · rare exomes 100/1,460,916 · genomes 7/152,358 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.221%	453
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.00167%	59,898
European (non-Finnish)	0.000254%	393,241

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.His412=
Coding: c.1236C>T
MANE Select: NM_024301
dbSNP: rs201076863
Type: single nucleotide variant
Location: chr19:46756686 (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.His412Gln Uncertain significance ★ ⚠ same residue
FKRP p.His412fs 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

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-his412 (accessed [today's date]).

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