Is POMT2 p.Pro290= (c.870C>T) pathogenic?

POMT2 p.Pro290= (c.870C>T) is classified Likely benign in POMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-13). Very rare (popmax 0.00534%, afr); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2.

What condition is associated with POMT2 p.Pro290= (c.870C>T)?

POMT2 p.Pro290= (c.870C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2, autosomal recessive limb-girdle muscular dystrophy type 2N (ClinVar).

How common is POMT2 p.Pro290= (c.870C>T) in the general population?

POMT2 p.Pro290= (c.870C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

POMT2 p.Pro290=

c.870C>T · rs1003348896 · VCV2935694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2

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 -2.4	GERP -3.2
Overall
CADD	5.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,912 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,614,006 alleles · very rare exomes 4/1,461,846 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,728
European (non-Finnish)	0.000254%	393,338

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.Pro290=
Coding: c.870C>T
MANE Select: NM_013382
dbSNP: rs1003348896
Type: single nucleotide variant
Location: chr14:77299508 (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

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 autosomal recessive limb-girdle muscular dystrophy type 2N

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

POMT2 p.Pro290Leu Uncertain significance ★ ⚠ same residue
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

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-pro290 (accessed [today's date]).

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