Is POMK p.Phe253= (c.759C>T) pathogenic?

POMK p.Phe253= (c.759C>T) is classified Likely benign in POMK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-15). Ultra-rare (popmax 0.075%, amr); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12.

How common is POMK p.Phe253= (c.759C>T) in the general population?

POMK p.Phe253= (c.759C>T) is ultra-rare (popmax 0.075%, amr) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

POMK p.Phe253=

Q: What condition is associated with POMK p.Phe253= (c.759C>T)?

POMK p.Phe253= (c.759C>T) 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.759C>T · rs201232766 · VCV436702

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.075%, 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 -4.7	GERP -2.2
Overall
CADD	4.589	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.075% Admixed American · 45/60,026 alleles

Filtering AF 0.0575% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0513%

Overall 0.00774% 125/1,614,212 alleles · ultra-rare exomes 82/1,461,884 · genomes 43/152,328 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.075%	1,334
South Asian	0.0318%	3,141
African / African-American	0.0266%	3,753
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.0022%	45,386
Finnishnot grpmax-eligible	0.00156%	64,036

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.Phe253=
Coding: c.759C>T
MANE Select: NM_032237
dbSNP: rs201232766
Type: single nucleotide variant
Location: chr8:43122583 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.62
Residue 253: the protein kinase domain

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-phe253 (accessed [today's date]).

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