Is MVK p.Pro11= (c.33G>A) pathogenic?

MVK p.Pro11= (c.33G>A) is classified Conflicting classifications of pathogenicity in MVK (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0892%, eas); Associated with mevalonic aciduria.

How common is MVK p.Pro11= (c.33G>A) in the general population?

MVK p.Pro11= (c.33G>A) is ultra-rare (popmax 0.0892%, eas) (gnomAD).

How is Mevalonate kinase deficiency inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

MVK p.Pro11=

Q: What condition is associated with MVK p.Pro11= (c.33G>A)?

MVK p.Pro11= (c.33G>A) is associated with mevalonic aciduria, porokeratosis 3, disseminated superficial actinic type, hyperimmunoglobulinemia D with periodic fever (ClinVar).

c.33G>A · rs779289416 · VCV882748

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0892%, eas)

Conditions

mevalonic aciduria

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 -6.9	GERP -2.7
Overall
CADD	3.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0892% East Asian · 40/44,838 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00286% 46/1,609,674 alleles · ultra-rare exomes 44/1,457,540 · genomes 2/152,134 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0892%	1,121
South Asian	0.00445%	22,484
Remaining individualsnot grpmax-eligible	0.0016%	62,360
European (non-Finnish)	8.49e-05%	1,178,064

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: MVK
Protein: p.Pro11=
Coding: c.33G>A
MANE Select: NM_000431
dbSNP: rs779289416
Type: single nucleotide variant
Location: chr12:109574855 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB
Residue 11: a β-strand

Full MVK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mevalonic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: porokeratosis 3, disseminated superficial actinic type hyperimmunoglobulinemia D with periodic fever inherited retinal dystrophy

For Mevalonate kinase deficiency (Orphanet):

Inheritance: Not applicable
Onset: Infancy

Similar variants

MVK p.Pro11Leu Uncertain significance ★★ ⚠ same residue
MVK p.Pro11Ser Uncertain significance ★★ ⚠ same residue
MVK c.1039+1G>C Likely pathogenic ★★ same condition
MVK c.677+1G>A Likely pathogenic ★★ same condition
MVK c.78+1G>A Likely pathogenic ★★ same condition
MVK c.79-2A>G Likely pathogenic ★★ same condition
MVK p.Ala147Thr Likely pathogenic ★★ same condition
MVK p.Ala148Thr Pathogenic/Likely pathogenic ★★ 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/mvk-p-pro11 (accessed [today's date]).

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