Is MPDZ p.Phe93Cys (c.278T>G) pathogenic?

MPDZ p.Phe93Cys (c.278T>G) is classified Benign/Likely benign in MPDZ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0956); Low-frequency (popmax 1.64%, afr).

How common is MPDZ p.Phe93Cys (c.278T>G) in the general population?

MPDZ p.Phe93Cys (c.278T>G) is low-frequency (popmax 1.64%, afr) (gnomAD).

What do computational predictors say about MPDZ p.Phe93Cys (c.278T>G)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

MPDZ p.Phe93Cys

c.278T>G · rs139373441 · VCV709856

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.72	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 2.7	GERP -2.1, phastCons 1
Overall
CADD	20.2	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 1.64% African / African-American · 1,227/74,942 alleles

Filtering AF 1.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.53%

Overall 0.0879% 1,418/1,612,810 alleles · low-frequency exomes 686/1,460,658 · genomes 732/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.64%	61
Admixed American	0.18%	554
Remaining individualsnot grpmax-eligible	0.111%	905
Middle Eastern	0.0165%	6,058
South Asian	0.00439%	22,766
European (non-Finnish)	0.000763%	131,022

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.Phe93Cys
Coding: c.278T>G
MANE Select: NM_001378778
dbSNP: rs139373441
Type: single nucleotide variant
Location: chr9:13224489 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 93: an α-helix

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

Similar variants

MPDZ p.Phe93Tyr Uncertain significance ★ ⚠ same residue
MPDZ p.Phe93= Likely benign ★ 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

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-phe93cys (accessed [today's date]).

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