Is POMT2 p.Val33= (c.99G>A) pathogenic?

POMT2 p.Val33= (c.99G>A) is classified Likely benign in POMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Very rare (popmax 0.000171%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2N.

How common is POMT2 p.Val33= (c.99G>A) in the general population?

POMT2 p.Val33= (c.99G>A) is very rare (popmax 0.000171%, nfe) (gnomAD).

How is POMT2-related limb-girdle muscular dystrophy R14 inherited?

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

POMT2 p.Val33=

Q: What condition is associated with POMT2 p.Val33= (c.99G>A)?

POMT2 p.Val33= (c.99G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2N, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (ClinVar).

c.99G>A · VCV3753532

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2N

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 1	GERP 0.31, phastCons 0.12
Overall
CADD	10.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,169,382 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000127% 2/1,578,072 alleles · very rare exomes 2/1,425,748 · genomes 0/152,324 · joint denominator

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: POMT2
Protein: p.Val33=
Coding: c.99G>A
MANE Select: NM_013382
Type: single nucleotide variant
Location: chr14:77320583 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.96

Full POMT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2

For POMT2-related limb-girdle muscular dystrophy R14 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

POMT2 c.1006+1G>A Pathogenic ★★ same condition
POMT2 c.1184-1G>C Likely pathogenic ★★ same condition
POMT2 c.1254-2A>G Likely pathogenic ★★ same condition
POMT2 c.1333-14G>A Pathogenic/Likely pathogenic ★★ same condition
POMT2 c.1786-2A>T Pathogenic/Likely pathogenic ★★ same condition
POMT2 c.248+1G>A Likely pathogenic ★★ same condition
POMT2 c.248+1G>C Pathogenic/Likely pathogenic ★★ same condition
POMT2 c.248+1G>T 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/pomt2-p-val33 (accessed [today's date]).

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