Is MVK p.Ter397= (c.1190G>A) pathogenic?

MVK p.Ter397= (c.1190G>A) is classified Likely benign in MVK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). No allele count reported in gnomAD v4.1 (AN 1,608,776); Associated with mevalonic aciduria.

How common is MVK p.Ter397= (c.1190G>A) in the general population?

MVK p.Ter397= (c.1190G>A) is no allele count reported in gnomAD v4.1 (AN 1,608,776) (gnomAD).

How is Mevalonate kinase deficiency inherited?

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

MVK p.Ter397=

Q: What condition is associated with MVK p.Ter397= (c.1190G>A)?

MVK p.Ter397= (c.1190G>A) is associated with mevalonic aciduria, porokeratosis 3, disseminated superficial actinic type, hyperimmunoglobulinemia D with periodic fever (ClinVar).

c.1190G>A · VCV3747908

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,776)

Conditions

mevalonic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.44, phastCons 1
Overall
CADD	10.91	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,608,776). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MVK
Protein: p.Ter397=
Coding: c.1190G>A
MANE Select: NM_000431
Type: single nucleotide variant
Location: chr12:109596576 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB

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 p.Ter397Arg Conflicting classifications of pathogenicity ★ 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
MVK p.Ala334Thr 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-ter397 (accessed [today's date]).

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