Is POMK p.Pro209= (c.627G>A) pathogenic?

POMK p.Pro209= (c.627G>A) is classified Likely benign in POMK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). Ultra-rare (popmax 0.011%, sas); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12.

How common is POMK p.Pro209= (c.627G>A) in the general population?

POMK p.Pro209= (c.627G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

POMK p.Pro209=

Q: What condition is associated with POMK p.Pro209= (c.627G>A)?

POMK p.Pro209= (c.627G>A) 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.627G>A · rs771102494 · VCV1567829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

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 0.57	GERP -2.2, phastCons 1
Overall
CADD	5.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,078 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00118% 19/1,613,978 alleles · ultra-rare exomes 18/1,461,818 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
East Asian	0.00668%	14,963
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000424%	236,005

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.Pro209=
Coding: c.627G>A
MANE Select: NM_032237
dbSNP: rs771102494
Type: single nucleotide variant
Location: chr8:43122451 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.62
Residue 209: 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.Pro209Leu 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-pro209 (accessed [today's date]).

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