MPDZ p.Val431=
c.1293A>G · rs759505437 · VCV2155906
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0313%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.67 | acceptor loss, 2 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.74 | GERP -4.7, phastCons 0.017 |
| Overall | ||
| CADD | 5.705 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0313%
South Asian · 26/82,986 alleles
Filtering AF
0.0219%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.00696%
109/1,567,086 alleles · ultra-rare
exomes 95/1,417,244 · genomes 14/149,842 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0313% | 3,192 |
| Middle Eastern | 0.017% | 5,898 |
| European (non-Finnish) | 0.00644% | 15,517 |
| Remaining individualsnot grpmax-eligible | 0.00495% | 20,216 |
| Admixed American | 0.00411% | 24,324 |
| Finnishnot grpmax-eligible | 0.00328% | 30,529 |
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.Val431=
- Coding
- c.1293A>G
- MANE Select
- NM_001378778
- dbSNP
- rs759505437
- Type
- single nucleotide variant
- Location
- chr9:13206097 (GRCh38)
- Structure
- AlphaFold pLDDT 72.11 · 3 PDB
- Residue 431
- the pdz 2 domain
Similar variants
- MPDZ p.Val431Ile 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-val431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown