Is MVK p.Ser69= (c.207A>G) pathogenic?

MVK p.Ser69= (c.207A>G) is classified Likely benign in MVK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-16). Absent from gnomAD v4.1; Associated with mevalonic aciduria.

How common is MVK p.Ser69= (c.207A>G) in the general population?

MVK p.Ser69= (c.207A>G) is absent from gnomAD v4.1 (gnomAD).

How is Mevalonate kinase deficiency inherited?

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

MVK p.Ser69=

Q: What condition is associated with MVK p.Ser69= (c.207A>G)?

MVK p.Ser69= (c.207A>G) is associated with mevalonic aciduria, porokeratosis 3, disseminated superficial actinic type, hyperimmunoglobulinemia D with periodic fever (ClinVar).

c.207A>G · rs2548618900 · VCV2942217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.021	GERP -0.54
Overall
CADD	3.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MVK
Protein: p.Ser69=
Coding: c.207A>G
MANE Select: NM_000431
dbSNP: rs2548618900
Type: single nucleotide variant
Location: chr12:109576126 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB
Residue 69: an α-helix

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

For Mevalonate kinase deficiency (Orphanet):

Inheritance: Not applicable
Onset: Infancy

Similar variants

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
MVK p.Ala334Thr Pathogenic ★★ same condition
MVK p.Arg215Gln 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-ser69 (accessed [today's date]).

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