Is POMT1 p.Trp186Ter (c.558G>A) pathogenic?

POMT1 p.Trp186Ter (c.558G>A) is classified Pathogenic in POMT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-09). Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2K.

What condition is associated with POMT1 p.Trp186Ter (c.558G>A)?

POMT1 p.Trp186Ter (c.558G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2K, muscular dystrophy-dystroglycanopathy, type A, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (ClinVar).

How common is POMT1 p.Trp186Ter (c.558G>A) in the general population?

POMT1 p.Trp186Ter (c.558G>A) is absent from gnomAD v4.1 (gnomAD).

How is POMT1-related limb-girdle muscular dystrophy R11 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

POMT1 p.Trp186Ter

c.558G>A · rs772370177 · VCV212739

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2K

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: POMT1
Protein: p.Trp186Ter
Coding: c.558G>A
MANE Select: NM_001077365
dbSNP: rs772370177
Type: single nucleotide variant
Location: chr9:131509761 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.09

Full POMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2K — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy, type A muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

For POMT1-related limb-girdle muscular dystrophy R11 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

POMT1 p.Trp186Cys Uncertain significance ★★ ⚠ same residue
POMT1 c.1175+1G>A Pathogenic ★★ same condition
POMT1 c.1176-2A>G Pathogenic/Likely pathogenic ★★ same condition
POMT1 c.1272+1G>A Pathogenic ★★ same condition
POMT1 c.1272+2T>C Pathogenic/Likely pathogenic ★★ same condition
POMT1 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same condition
POMT1 c.2004-1G>C Pathogenic/Likely pathogenic ★★ same condition
POMT1 c.229+2T>C 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/pomt1-p-trp186ter (accessed [today's date]).

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