Is MVK p.Pro127= (c.381G>A) pathogenic?

MVK p.Pro127= (c.381G>A) is classified Benign/Likely benign in MVK (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-31). Rare (popmax 0.61%, afr); Associated with autoinflammatory syndrome.

How common is MVK p.Pro127= (c.381G>A) in the general population?

MVK p.Pro127= (c.381G>A) is rare (popmax 0.61%, afr) (gnomAD).

MVK p.Pro127=

Q: What condition is associated with MVK p.Pro127= (c.381G>A)?

MVK p.Pro127= (c.381G>A) is associated with autoinflammatory syndrome, porokeratosis 3, disseminated superficial actinic type, hyperimmunoglobulinemia D with periodic fever (ClinVar).

c.381G>A · rs140397628 · VCV138313

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.61%, afr)

Conditions

autoinflammatory syndrome

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 -2.9	GERP -3
Overall
CADD	8.957	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.61% African / African-American · 458/75,044 alleles

Filtering AF 0.564% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.546%

Overall 0.0343% 554/1,613,936 alleles · rare exomes 271/1,461,662 · genomes 283/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.61%	164
Middle Eastern	0.169%	593
Admixed American	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0336%	2,975
South Asian	0.00549%	18,212
European (non-Finnish)	0.00271%	36,875
East Asian	0.00223%	44,862

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.Pro127=
Coding: c.381G>A
MANE Select: NM_000431
dbSNP: rs140397628
Type: single nucleotide variant
Location: chr12:109581404 (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

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: porokeratosis 3, disseminated superficial actinic type hyperimmunoglobulinemia D with periodic fever mevalonic aciduria

Similar variants

MVK p.Pro127Leu 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-pro127 (accessed [today's date]).

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