Is MVD p.Arg78= (c.232C>A) pathogenic?

MVD p.Arg78= (c.232C>A) is classified Benign in MVD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-09-05). Common (popmax 74.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with porokeratosis 7, multiple types.

What condition is associated with MVD p.Arg78= (c.232C>A)?

MVD p.Arg78= (c.232C>A) is associated with porokeratosis 7, multiple types (ClinVar).

MVD p.Arg78=

Q: How common is MVD p.Arg78= (c.232C>A) in the general population?

MVD p.Arg78= (c.232C>A) is common (popmax 74.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Disseminated superficial actinic porokeratosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.232C>A · rs2279258 · VCV1321178

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 74.5%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

porokeratosis 7, multiple types

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 7.3	GERP 1.9, phastCons 1
Overall
CADD	11.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 74.5% Admixed American · 44,688/60,012 alleles

Filtering AF 73.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 73.6%

Overall 62.6% 1,010,494/1,613,370 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	74.5%	1
Finnishnot grpmax-eligible	69.4%	1
Amishnot grpmax-eligible	68.5%	1
European (non-Finnish)	65.5%	2
Remaining individualsnot grpmax-eligible	60.5%	2
East Asian	60.1%	2
Ashkenazi Jewishnot grpmax-eligible	57.9%	2
Middle Eastern	57.4%	2
South Asian	42.3%	2
African / African-American	31.8%	3

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: MVD
Protein: p.Arg78=
Coding: c.232C>A
MANE Select: NM_002461
dbSNP: rs2279258
Type: single nucleotide variant
Location: chr16:88657939 (GRCh38)
Gene constraint: LOEUF 1.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.52 · 1 PDB
Residue 78: an α-helix; a binding site

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

Disease context

porokeratosis 7, multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Disseminated superficial actinic porokeratosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

MVD p.Arg78Gln Uncertain significance ★ ⚠ same residue
MVD p.Phe249Ser Pathogenic ★★ same condition
MVD c.1013+1G>T Pathogenic ★ same condition
MVD c.1014-1G>T Likely pathogenic ★ same condition
MVD p.Asn292Ser Pathogenic ★ ⚠ same condition
MVD c.1013+5G>T Uncertain significance ★ same condition
MVD c.604-7C>T Uncertain significance ★ same condition
MVD p.Glu230Lys Conflicting classifications of pathogenicity ★ ⚠ 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/mvd-p-arg78 (accessed [today's date]).

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