Is GMPPB p.Ser54Arg (c.160A>C) pathogenic?

GMPPB p.Ser54Arg (c.160A>C) is classified Uncertain significance in GMPPB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-12-09). AlphaMissense: likely pathogenic (0.9824); Ultra-rare (popmax 0.0254%, nfe); Associated with Inborn genetic diseases.

How common is GMPPB p.Ser54Arg (c.160A>C) in the general population?

GMPPB p.Ser54Arg (c.160A>C) is ultra-rare (popmax 0.0254%, nfe) (gnomAD).

What do computational predictors say about GMPPB p.Ser54Arg (c.160A>C)?

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

GMPPB p.Ser54Arg

Q: What condition is associated with GMPPB p.Ser54Arg (c.160A>C)?

GMPPB p.Ser54Arg (c.160A>C) is associated with Inborn genetic diseases, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 (ClinVar).

c.160A>C · rs145671483 · VCV664971

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9824 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9824	likely pathogenic
REVEL	0.736	pathogenic-leaning
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,971 bp · p 0.021 · regional, not allelic
Overall
CADD	24.8	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

Grpmax group 0.0254% European (non-Finnish) · 300/1,180,042 alleles

Filtering AF 0.023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0221%

Overall 0.0202% 326/1,613,894 alleles · ultra-rare exomes 319/1,461,720 · genomes 7/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0254%	3,933
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0112%	8,926
Admixed American	0.00833%	12,001
South Asian	0.00768%	13,013
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
East Asian	0.00445%	22,447
African / African-American	0.00267%	37,457

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.Ser54Arg
Coding: c.160A>C
MANE Select: NM_021971
dbSNP: rs145671483
Type: single nucleotide variant
Location: chr3:49723442 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 54: the 'substrate-binding domain' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 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-ser54arg (accessed [today's date]).

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