Is MPDU1 p.Val28Ile (c.82G>A) pathogenic?

MPDU1 p.Val28Ile (c.82G>A) is classified Uncertain significance in MPDU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with MPDU1 p.Val28Ile (c.82G>A)?

MPDU1 p.Val28Ile (c.82G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MPDU1 p.Val28Ile (c.82G>A) in the general population?

MPDU1 p.Val28Ile (c.82G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about MPDU1 p.Val28Ile (c.82G>A)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

MPDU1 p.Val28Ile

c.82G>A · VCV3912591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.82, phastCons 0.016
Regional constraint	o/e 0.94	unconstrained · MANE · 3,685 bp · p 0.29 · regional, not allelic
Overall
CADD	16.82	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00112% 18/1,614,006 alleles · ultra-rare exomes 16/1,461,778 · genomes 2/152,228 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00144%	69,415

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: MPDU1
Protein: p.Val28Ile
Coding: c.82G>A
MANE Select: NM_004870
Type: single nucleotide variant
Location: chr17:7583944 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57

Full MPDU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPDU1 p.Val28= Uncertain significance ★ same residue
MPDU1 p.Arg200Gln Uncertain significance ★★ ⚠ same condition
MPDU1 p.Thr113Met Uncertain significance ★★ ⚠ same condition
MPDU1 c.169+4T>G Uncertain significance ★ same condition
MPDU1 p.Ala228Thr Uncertain significance ★ ⚠ same condition
MPDU1 p.Ala52Ser Uncertain significance ★ ⚠ same condition
MPDU1 p.Asn161Ser Uncertain significance ★ ⚠ same condition
MPDU1 p.Asp31His Uncertain significance ★ 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/mpdu1-p-val28ile (accessed [today's date]).

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