Is MPST p.Asp93Val (c.278A>T) pathogenic?

MPST p.Asp93Val (c.278A>T) is classified Uncertain significance in MPST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: ambiguous (0.4929); Very rare (popmax 0.00194%, amr).

How common is MPST p.Asp93Val (c.278A>T) in the general population?

MPST p.Asp93Val (c.278A>T) is very rare (popmax 0.00194%, amr) (gnomAD).

What do computational predictors say about MPST p.Asp93Val (c.278A>T)?

AlphaMissense predicts ambiguous (score 0.4929) — an in-silico prediction, not a clinical call.

MPST p.Asp93Val

c.278A>T · rs761967107 · VCV2243341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00194%, amr)

Computational evidence

Protein change
AlphaMissense	0.4929	ambiguous
REVEL	0.489	indeterminate
SaProt	LLR -11.45	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 9,674 bp · p 0.34 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D73V vs ClinVar D93V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00194% Admixed American · 1/51,646 alleles

Overall 6.47e-05% 1/1,544,892 alleles · very rare exomes 1/1,392,644 · genomes 0/152,248 · 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: MPST
Protein: p.Asp93Val
Coding: c.278A>T
MANE Select: NM_021126
dbSNP: rs761967107
Type: single nucleotide variant
Location: chr22:37024433 (GRCh38)
Gene constraint: LOEUF 1.501 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.74 · 2 PDB
Residue 73 UniProt numbering: the rhodanese 1 domain; a β-strand

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

Similar variants

MPST p.Ala103Glu Uncertain significance ★ ⚠ same type
MPST p.Ala130Val Uncertain significance ★ ⚠ same type
MPST p.Ala19Ser Uncertain significance ★ same type
MPST p.Ala303Val Uncertain significance ★ same type
MPST p.Ala33Val Uncertain significance ★ ⚠ same type
MPST p.Ala39Val Uncertain significance ★ ⚠ same type
MPST p.Ala45Ser Uncertain significance ★ ⚠ same type
MPST p.Ala77Val Uncertain significance ★ ⚠ 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/mpst-p-asp93val (accessed [today's date]).

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