Is MVK p.Pro54= (c.162C>T) pathogenic?

MVK p.Pro54= (c.162C>T) is classified Likely benign in MVK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-12). Very rare (popmax 8.47e-05%, nfe); Associated with porokeratosis 3, disseminated superficial actinic type.

What condition is associated with MVK p.Pro54= (c.162C>T)?

MVK p.Pro54= (c.162C>T) is associated with porokeratosis 3, disseminated superficial actinic type, hyperimmunoglobulinemia D with periodic fever, mevalonic aciduria (ClinVar).

How common is MVK p.Pro54= (c.162C>T) in the general population?

MVK p.Pro54= (c.162C>T) is very rare (popmax 8.47e-05%, nfe) (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.Pro54=

c.162C>T · rs2136218809 · VCV1635160

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.99	GERP -3.3
Overall
CADD	5.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.2e-05% 1/1,614,164 alleles · very rare exomes 1/1,461,866 · genomes 0/152,298 · joint denominator

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.Pro54=
Coding: c.162C>T
MANE Select: NM_000431
dbSNP: rs2136218809
Type: single nucleotide variant
Location: chr12:109576081 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB
Residue 54: a turn

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-pro54 (accessed [today's date]).

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