Is MPDZ p.Ile665= (c.1995C>T) pathogenic?

MPDZ p.Ile665= (c.1995C>T) is classified Benign/Likely benign in MPDZ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-22). Rare (popmax 0.668%, eas).

How common is MPDZ p.Ile665= (c.1995C>T) in the general population?

MPDZ p.Ile665= (c.1995C>T) is rare (popmax 0.668%, eas) (gnomAD).

MPDZ p.Ile665=

c.1995C>T · rs181658884 · VCV782117

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.668%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.20	loss · gain 0.02 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.86	GERP -4.3
Overall
CADD	2.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.668% East Asian · 298/44,638 alleles

Filtering AF 0.605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.121% 1,939/1,603,046 alleles · rare exomes 1,713/1,450,922 · genomes 226/152,124 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.41%	71
East Asiangrpmax	0.668%	150
Ashkenazi Jewishnot grpmax-eligible	0.543%	184
Remaining individualsnot grpmax-eligible	0.175%	570
African / African-American	0.0522%	1,916
European (non-Finnish)	0.0374%	2,677
South Asian	0.018%	5,558
Middle Eastern	0.0167%	5,986
Admixed American	0.00339%	29,511

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile665=
Coding: c.1995C>T
MANE Select: NM_001378778
dbSNP: rs181658884
Type: single nucleotide variant
Location: chr9:13190273 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 665: the pdz 4 domain

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

Similar variants

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
MPDZ p.Arg1170Ter 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-ile665 (accessed [today's date]).

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