Is GMPPB p.Ser267= (c.801C>T) pathogenic?

GMPPB p.Ser267= (c.801C>T) is classified Likely benign in GMPPB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-15). Very rare (popmax 0.00161%, nfe); Associated with muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14.

What condition is associated with GMPPB p.Ser267= (c.801C>T)?

GMPPB p.Ser267= (c.801C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, autosomal recessive limb-girdle muscular dystrophy type 2T (ClinVar).

How common is GMPPB p.Ser267= (c.801C>T) in the general population?

GMPPB p.Ser267= (c.801C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

GMPPB p.Ser267=

c.801C>T · rs752457623 · VCV1570903

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.39, phastCons 1
Overall
CADD	8.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,784 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,613,166 alleles · very rare exomes 18/1,460,916 · genomes 2/152,250 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,094
African / African-American	0.00133%	74,938

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: GMPPB
Protein: p.Ser267=
Coding: c.801C>T
MANE Select: NM_021971
dbSNP: rs752457623
Type: single nucleotide variant
Location: chr3:49722115 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 267: the 'hexapeptide repeat domain' region

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

Disease context

muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 autosomal recessive limb-girdle muscular dystrophy type 2T

Similar variants

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 c.640+1G>C 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
GMPPB p.Asp27His 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/gmppb-p-ser267 (accessed [today's date]).

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