Is MVD p.Cys386= (c.1158C>T) pathogenic?

MVD p.Cys386= (c.1158C>T) is classified Likely benign in MVD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-02). Very rare (popmax 0.00468%, sas).

How common is MVD p.Cys386= (c.1158C>T) in the general population?

MVD p.Cys386= (c.1158C>T) is very rare (popmax 0.00468%, sas) (gnomAD).

MVD p.Cys386=

c.1158C>T · VCV4931737

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00468%, sas)

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 -14	GERP -2.9
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00468% South Asian · 4/85,558 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000989%

Overall 0.00178% 28/1,570,462 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00468%	21,390
Remaining individualsnot grpmax-eligible	0.00329%	30,410
Admixed American	0.00185%	54,164
European (non-Finnish)	0.00181%	55,138

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.Cys386=
Coding: c.1158C>T
MANE Select: NM_002461
Type: single nucleotide variant
Location: chr16:88652570 (GRCh38)
Gene constraint: LOEUF 1.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.52 · 1 PDB
Residue 386: an α-helix

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

Similar variants

MVD p.Phe249Ser Pathogenic ★★ same type
MVD p.Thr120Met Uncertain significance ★★ ⚠ same type
MVD p.Arg78= Benign ★★ same type
MVD p.Lys368= Benign/Likely benign ★★ same type
MVD p.Pro77= Benign ★★ same type
MVD c.1013+1G>T Pathogenic ★ same type
MVD c.1014-1G>T Likely pathogenic ★ same type
MVD p.Asn292Ser Pathogenic ★ ⚠ same type

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-cys386 (accessed [today's date]).

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