Is MPDZ p.Val2016Ile (c.6046G>A) pathogenic?

MPDZ p.Val2016Ile (c.6046G>A) is classified Uncertain significance in MPDZ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-03). AlphaMissense: likely benign (0.131); Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with MPDZ p.Val2016Ile (c.6046G>A)?

MPDZ p.Val2016Ile (c.6046G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MPDZ p.Val2016Ile (c.6046G>A) in the general population?

MPDZ p.Val2016Ile (c.6046G>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about MPDZ p.Val2016Ile (c.6046G>A)?

AlphaMissense predicts likely benign (score 0.131) — an in-silico prediction, not a clinical call.

MPDZ p.Val2016Ile

c.6046G>A · rs755736030 · VCV1925243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.131 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.131	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP 2.4, phastCons 0.96
Overall
CADD	22.3	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 0.00668% African / African-American · 5/74,880 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000435% 7/1,610,688 alleles · very rare exomes 7/1,458,522 · genomes 0/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,976
Remaining individualsnot grpmax-eligible	0.00321%	31,158

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: MPDZ
Protein: p.Val2016Ile
Coding: c.6046G>A
MANE Select: NM_001378778
dbSNP: rs755736030
Type: single nucleotide variant
Location: chr9:13108956 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB

Full MPDZ 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

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MPDZ c.5558-3C>T Uncertain significance ★★ same condition
MPDZ p.Ala104Thr Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala1068Asp Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala10Val Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala1196Gly Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala1227Thr 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/mpdz-p-val2016ile (accessed [today's date]).

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