Is MPDZ p.Pro690Ala (c.2068C>G) pathogenic?

MPDZ p.Pro690Ala (c.2068C>G) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely benign (0.0763); Very rare (popmax 0.00668%, afr).

How common is MPDZ p.Pro690Ala (c.2068C>G) in the general population?

MPDZ p.Pro690Ala (c.2068C>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about MPDZ p.Pro690Ala (c.2068C>G)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

MPDZ p.Pro690Ala

c.2068C>G · rs764453158 · VCV1404707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.74	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 6.6	GERP 2.2, phastCons 1
Overall
CADD	21.5	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 0.00668% African / African-American · 5/74,860 alleles

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

Overall 0.000434% 7/1,613,066 alleles · very rare exomes 5/1,460,974 · genomes 2/152,092 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,972
Remaining individualsnot grpmax-eligible	0.0032%	31,220

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.Pro690Ala
Coding: c.2068C>G
MANE Select: NM_001378778
dbSNP: rs764453158
Type: single nucleotide variant
Location: chr9:13190200 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 690: the pdz 4 domain

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

Similar variants

MPDZ p.Pro690Arg Uncertain significance ★ ⚠ same residue
MPDZ c.1087-1G>A Pathogenic/Likely pathogenic ★★ same type
MPDZ c.1474+2T>C Likely pathogenic ★★ same type
MPDZ c.3359+1G>A Likely pathogenic ★★ same type
MPDZ c.3360-2A>G Pathogenic/Likely pathogenic ★★ same type
MPDZ c.4003+1G>A Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Arg1034Ter Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Arg1071Ter 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/mpdz-p-pro690ala (accessed [today's date]).

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