Is MVK p.Cys367= (c.1101C>T) pathogenic?

MVK p.Cys367= (c.1101C>T) is classified Likely benign in MVK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). Absent from gnomAD v4.1; Associated with porokeratosis 3, disseminated superficial actinic type.

What condition is associated with MVK p.Cys367= (c.1101C>T)?

MVK p.Cys367= (c.1101C>T) is associated with porokeratosis 3, disseminated superficial actinic type, hyperimmunoglobulinemia D with periodic fever, mevalonic aciduria (ClinVar).

How common is MVK p.Cys367= (c.1101C>T) in the general population?

MVK p.Cys367= (c.1101C>T) is absent from gnomAD v4.1 (gnomAD).

How is Porokeratosis of Mibelli inherited?

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

MVK p.Cys367=

c.1101C>T · rs2548642905 · VCV2921663

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

porokeratosis 3, disseminated superficial actinic type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	GERP -0.47, phastCons 1
Overall
CADD	10.7	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.Cys367=
Coding: c.1101C>T
MANE Select: NM_000431
dbSNP: rs2548642905
Type: single nucleotide variant
Location: chr12:109596487 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB
Residue 367: a β-strand

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

Disease context

porokeratosis 3, disseminated superficial actinic type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperimmunoglobulinemia D with periodic fever mevalonic aciduria

For Porokeratosis of Mibelli (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood

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-cys367 (accessed [today's date]).

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