Is POMK p.Ser48Pro (c.142T>C) pathogenic?

POMK p.Ser48Pro (c.142T>C) is classified Likely benign in POMK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-05). AlphaMissense: likely benign (0.0614); Rare (popmax 0.448%, eas); Associated with limb-girdle muscular dystrophy due to POMK deficiency.

What condition is associated with POMK p.Ser48Pro (c.142T>C)?

POMK p.Ser48Pro (c.142T>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.Ser48Pro (c.142T>C) in the general population?

POMK p.Ser48Pro (c.142T>C) is rare (popmax 0.448%, eas) (gnomAD).

What do computational predictors say about POMK p.Ser48Pro (c.142T>C)?

AlphaMissense predicts likely benign (score 0.0614) — an in-silico prediction, not a clinical call.

POMK p.Ser48Pro

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.142T>C · rs34466747 · VCV474189

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0614 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.448%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

limb-girdle muscular dystrophy due to POMK deficiency

Computational evidence

Protein change
AlphaMissense	0.0614	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3.9
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.31 · regional, not allelic
Overall
CADD	0.054	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.448% East Asian · 201/44,846 alleles

Filtering AF 0.397% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.378%

Overall 0.0126% 204/1,613,906 alleles · rare exomes 189/1,461,886 · genomes 15/152,020 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.448%	223
Remaining individualsnot grpmax-eligible	0.0048%	20,834

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.Ser48Pro
Coding: c.142T>C
MANE Select: NM_032237
dbSNP: rs34466747
Type: single nucleotide variant
Location: chr8:43103690 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.62
Residue 48: a UniProt-annotated variant site (in)

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.Ser48Cys Uncertain significance ★ ⚠ same residue
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

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-ser48pro (accessed [today's date]).

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