Is POMK p.Pro196= (c.588T>C) pathogenic?

POMK p.Pro196= (c.588T>C) is classified Likely benign in POMK (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-10). Very rare (popmax 0.00534%, afr); Associated with limb-girdle muscular dystrophy due to POMK deficiency.

What condition is associated with POMK p.Pro196= (c.588T>C)?

POMK p.Pro196= (c.588T>C) is associated with limb-girdle muscular dystrophy due to POMK deficiency, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (ClinVar).

How common is POMK p.Pro196= (c.588T>C) in the general population?

POMK p.Pro196= (c.588T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

POMK p.Pro196=

Q: How is Limb-girdle muscular dystrophy due to POMK deficiency inherited?

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

c.588T>C · rs766337800 · VCV761753

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

limb-girdle muscular dystrophy due to POMK deficiency

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 -2.8	GERP -1.2
Overall
CADD	0.969	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,954 alleles

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

Overall 0.000372% 6/1,614,100 alleles · very rare exomes 5/1,461,856 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,738
European (non-Finnish)	0.000169%	590,019

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: POMK
Protein: p.Pro196=
Coding: c.588T>C
MANE Select: NM_032237
dbSNP: rs766337800
Type: single nucleotide variant
Location: chr8:43122412 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.62
Residue 196: the protein kinase domain

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

Disease context

limb-girdle muscular dystrophy due to POMK deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12

For Limb-girdle muscular dystrophy due to POMK deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

POMK p.Arg15Ter Pathogenic ★★ same condition
POMK p.Arg303Ter Pathogenic/Likely pathogenic ★★ same condition
POMK p.Gln109Ter Pathogenic/Likely pathogenic ★★ same condition
POMK p.Gln4Ter Pathogenic/Likely pathogenic ★★ same condition
POMK p.Ala13Thr Uncertain significance ★★ ⚠ same condition
POMK p.Ala230Thr Uncertain significance ★★ same condition
POMK p.Ala28Ser Uncertain significance ★★ ⚠ same condition
POMK p.Arg15Leu Uncertain significance ★★ ⚠ 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/pomk-p-pro196 (accessed [today's date]).

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