Is POMK p.Ser73= (c.219C>G) pathogenic?

POMK p.Ser73= (c.219C>G) is classified Likely benign in POMK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.035%, amr); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12.

How common is POMK p.Ser73= (c.219C>G) in the general population?

POMK p.Ser73= (c.219C>G) is ultra-rare (popmax 0.035%, amr) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

POMK p.Ser73=

Q: What condition is associated with POMK p.Ser73= (c.219C>G)?

POMK p.Ser73= (c.219C>G) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12, limb-girdle muscular dystrophy due to POMK deficiency (ClinVar).

c.219C>G · rs188920070 · VCV541244

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Conditions

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

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 -0.029	GERP -3.9, phastCons 0.76
Overall
CADD	7.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/60,030 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.011% 178/1,614,216 alleles · ultra-rare exomes 163/1,461,882 · genomes 15/152,334 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,859
European (non-Finnish)	0.0128%	7,815
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00266%	37,534

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.Ser73=
Coding: c.219C>G
MANE Select: NM_032237
dbSNP: rs188920070
Type: single nucleotide variant
Location: chr8:43103767 (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

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: limb-girdle muscular dystrophy due to POMK deficiency

For Walker-Warburg syndrome (Orphanet):

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

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-ser73 (accessed [today's date]).

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