Is GMPPB p.Pro103Leu (c.308C>T) pathogenic?

GMPPB p.Pro103Leu (c.308C>T) is classified Likely pathogenic in GMPPB (ClinVar, Single submitter, 2 submitters; last evaluated 2021-07-10). AlphaMissense: likely benign (0.3209); Absent from gnomAD v4.1; Associated with Abnormality of the musculature.

What condition is associated with GMPPB p.Pro103Leu (c.308C>T)?

GMPPB p.Pro103Leu (c.308C>T) is associated with Abnormality of the musculature, autosomal recessive limb-girdle muscular dystrophy type 2T (ClinVar).

How common is GMPPB p.Pro103Leu (c.308C>T) in the general population?

GMPPB p.Pro103Leu (c.308C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GMPPB p.Pro103Leu (c.308C>T)?

AlphaMissense predicts likely benign (score 0.3209) — an in-silico prediction, not a clinical call.

GMPPB p.Pro103Leu

c.308C>T · rs875989851 · VCV225927

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3209 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Abnormality of the musculature

Computational evidence

Protein change
AlphaMissense	0.3209	likely benign ⚠ discordant with ClinVar
REVEL	0.74	pathogenic-leaning
SaProt	LLR -11.18	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,971 bp · p 0.021 · regional, not allelic
Overall
CADD	25.8	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: GMPPB
Protein: p.Pro103Leu
Coding: c.308C>T
MANE Select: NM_021971
dbSNP: rs875989851
Type: single nucleotide variant
Location: chr3:49723066 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 103: the 'substrate-binding domain' region

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

Disease context

Abnormality of the musculature — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2T

Similar variants

GMPPB p.Pro103= Likely benign ★★ same residue
GMPPB p.Pro103His Uncertain significance ★ ⚠ same residue
GMPPB c.129+1G>T Likely pathogenic ★★ same condition
GMPPB c.402+1G>A Pathogenic/Likely pathogenic ★★ same condition
GMPPB c.640+1G>A Pathogenic/Likely pathogenic ★★ same condition
GMPPB p.Arg185Cys Pathogenic/Likely pathogenic ★★ same condition
GMPPB p.Arg287Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
GMPPB p.Arg287Trp 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/gmppb-p-pro103leu (accessed [today's date]).

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