Is POMK p.Pro18= (c.54G>A) pathogenic?

POMK p.Pro18= (c.54G>A) is classified Likely benign in POMK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-29). Ultra-rare (popmax 0.012%, afr); Associated with limb-girdle muscular dystrophy due to POMK deficiency.

What condition is associated with POMK p.Pro18= (c.54G>A)?

POMK p.Pro18= (c.54G>A) 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.Pro18= (c.54G>A) in the general population?

POMK p.Pro18= (c.54G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

POMK p.Pro18=

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.54G>A · rs201226142 · VCV508002

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4	GERP -3.6
Overall
CADD	6.374	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,796 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00446% 72/1,613,724 alleles · ultra-rare exomes 57/1,461,848 · genomes 15/151,876 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,311
European (non-Finnish)	0.00517%	19,344
East Asian	0.00223%	44,872
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Pro18=
Coding: c.54G>A
MANE Select: NM_032237
dbSNP: rs201226142
Type: single nucleotide variant
Location: chr8:43103602 (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.Pro18Leu 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-pro18 (accessed [today's date]).

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