Is POMK p.Pro52Ser (c.154C>T) pathogenic?

POMK p.Pro52Ser (c.154C>T) is classified Uncertain significance in POMK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: likely benign (0.0726); Very rare (popmax 8.47e-05%, nfe); Associated with limb-girdle muscular dystrophy due to POMK deficiency.

What condition is associated with POMK p.Pro52Ser (c.154C>T)?

POMK p.Pro52Ser (c.154C>T) 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.Pro52Ser (c.154C>T) in the general population?

POMK p.Pro52Ser (c.154C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about POMK p.Pro52Ser (c.154C>T)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

POMK p.Pro52Ser

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.154C>T · rs1811491419 · VCV1960878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

limb-girdle muscular dystrophy due to POMK deficiency

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -5.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.3	GERP -1.1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.31 · regional, not allelic
Overall
CADD	7.589	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.2e-05% 1/1,614,144 alleles · very rare exomes 1/1,461,890 · genomes 0/152,254 · 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: POMK
Protein: p.Pro52Ser
Coding: c.154C>T
MANE Select: NM_032237
dbSNP: rs1811491419
Type: single nucleotide variant
Location: chr8:43103702 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.62

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-pro52ser (accessed [today's date]).

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