Is MPDZ p.Ser1830Phe (c.5489C>T) pathogenic?

MPDZ p.Ser1830Phe (c.5489C>T) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.2695); Very rare (popmax 8.54e-05%, nfe).

How common is MPDZ p.Ser1830Phe (c.5489C>T) in the general population?

MPDZ p.Ser1830Phe (c.5489C>T) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about MPDZ p.Ser1830Phe (c.5489C>T)?

AlphaMissense predicts likely benign (score 0.2695) — an in-silico prediction, not a clinical call.

MPDZ p.Ser1830Phe

c.5489C>T · rs1467827996 · VCV1449915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2695	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -10.25	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 10	GERP 2.4, phastCons 1
Overall
CADD	25.1	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 8.54e-05% European (non-Finnish) · 1/1,170,842 alleles

Overall 6.26e-05% 1/1,596,380 alleles · very rare exomes 0/1,444,162 · genomes 1/152,218 · joint denominator

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.Ser1830Phe
Coding: c.5489C>T
MANE Select: NM_001378778
dbSNP: rs1467827996
Type: single nucleotide variant
Location: chr9:13113999 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB

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

Similar variants

MPDZ p.Ser1830Pro 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-ser1830phe (accessed [today's date]).

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