Is FKRP p.Pro315Arg (c.944C>G) pathogenic?

FKRP p.Pro315Arg (c.944C>G) is classified Likely pathogenic in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely pathogenic (0.9824); Absent from gnomAD v4.1; Associated with FKRP-related disorder.

What condition is associated with FKRP p.Pro315Arg (c.944C>G)?

FKRP p.Pro315Arg (c.944C>G) is associated with FKRP-related disorder (ClinVar).

How common is FKRP p.Pro315Arg (c.944C>G) in the general population?

FKRP p.Pro315Arg (c.944C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FKRP p.Pro315Arg (c.944C>G)?

AlphaMissense predicts likely pathogenic (score 0.9824) — an in-silico prediction, not a clinical call.

FKRP p.Pro315Arg

c.944C>G · VCV4942971

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9824 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FKRP-related disorder

Computational evidence

Protein change
AlphaMissense	0.9824	likely pathogenic ✓ concordant with ClinVar · top 8% in FKRP
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -15.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FKRP
Protein: p.Pro315Arg
Coding: c.944C>G
MANE Select: NM_024301
Type: single nucleotide variant
Location: chr19:46756394 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 315: a UniProt-annotated variant site (in mddgb5; severe form; brain involvement; intellectual disability and cerebellar cysts on cranial mri); the 'zinc finger loop' region

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

Disease context

FKRP-related disorder

Similar variants

FKRP p.Pro315Thr Likely pathogenic ★ same residue
FKRP p.Pro315Ala Uncertain significance ★ ⚠ same residue
FKRP p.Pro315Ser Uncertain significance ★ ⚠ same residue
FKRP p.Pro315= Likely benign ★ same residue
FKRP p.Pro89Ser Likely pathogenic ★★ same condition
FKRP p.Ter496Arg Pathogenic/Likely pathogenic ★★ same condition
FKRP p.Ala326Asp Likely pathogenic ★ same condition
FKRP p.Trp286Arg 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-pro315arg (accessed [today's date]).

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