Is FKRP p.Pro315Ser (c.943C>T) pathogenic?

FKRP p.Pro315Ser (c.943C>T) is classified Uncertain significance in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely pathogenic (0.9563); No allele count reported in gnomAD v4.1 (AN 1,567,802).

How common is FKRP p.Pro315Ser (c.943C>T) in the general population?

FKRP p.Pro315Ser (c.943C>T) is no allele count reported in gnomAD v4.1 (AN 1,567,802) (gnomAD).

What do computational predictors say about FKRP p.Pro315Ser (c.943C>T)?

AlphaMissense predicts likely pathogenic (score 0.9563) — an in-silico prediction, not a clinical call.

FKRP p.Pro315Ser

c.943C>T · VCV3768480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9563 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,567,802)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9563	likely pathogenic
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -11.40	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 5.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,484 bp · p 0.11 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,567,802). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FKRP
Protein: p.Pro315Ser
Coding: c.943C>T
MANE Select: NM_024301
Type: single nucleotide variant
Location: chr19:46756393 (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

Similar variants

FKRP p.Pro315Arg Likely pathogenic ★ same residue
FKRP p.Pro315Thr Likely pathogenic ★ same residue
FKRP p.Pro315Ala Uncertain significance ★ ⚠ same residue
FKRP p.Pro315= Likely benign ★ same residue
FKRP p.Ala157Pro Pathogenic/Likely pathogenic ★★ same type
FKRP p.Ala321Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
FKRP p.Ala455Asp Pathogenic ★★ same type
FKRP p.Arg176Ter Pathogenic/Likely pathogenic ★★ same type

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-pro315ser (accessed [today's date]).

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