Is MVD p.Leu148Phe (c.442C>T) pathogenic?

MVD p.Leu148Phe (c.442C>T) is classified Uncertain significance in MVD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.1796); Very rare (popmax 0.00636%, nfe).

How common is MVD p.Leu148Phe (c.442C>T) in the general population?

MVD p.Leu148Phe (c.442C>T) is very rare (popmax 0.00636%, nfe) (gnomAD).

What do computational predictors say about MVD p.Leu148Phe (c.442C>T)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

MVD p.Leu148Phe

c.442C>T · VCV3297077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.727	pathogenic-leaning
SaProt	LLR -8.88	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.44, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 11 kb · p 0.00014 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00636% European (non-Finnish) · 75/1,179,930 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.005% 80/1,600,122 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,732
African / African-American	0.004%	24,977
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,398

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.Leu148Phe
Coding: c.442C>T
MANE Select: NM_002461
Type: single nucleotide variant
Location: chr16:88656266 (GRCh38)
Gene constraint: LOEUF 1.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.52 · 1 PDB

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-leu148phe (accessed [today's date]).

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