Is MPST p.Ala33Val (c.98C>T) pathogenic?

MPST p.Ala33Val (c.98C>T) is classified Uncertain significance in MPST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.1845); Very rare (popmax 0.00277%, eas).

How common is MPST p.Ala33Val (c.98C>T) in the general population?

MPST p.Ala33Val (c.98C>T) is very rare (popmax 0.00277%, eas) (gnomAD).

What do computational predictors say about MPST p.Ala33Val (c.98C>T)?

AlphaMissense predicts likely benign (score 0.1845) — an in-silico prediction, not a clinical call.

MPST p.Ala33Val

c.98C>T · rs940318746 · VCV2253645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00277%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1845	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -8.06	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 4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 9,674 bp · p 0.34 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A13V vs ClinVar A33V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00277% East Asian · 1/36,154 alleles

Filtering AF 0.000195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000128%

Overall 0.000555% 8/1,440,246 alleles · very rare exomes 7/1,288,104 · genomes 1/152,142 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00277%	36,154
Remaining individualsnot grpmax-eligible	0.0018%	55,500
European (non-Finnish)	0.000542%	184,413

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.Ala33Val
Coding: c.98C>T
MANE Select: NM_021126
dbSNP: rs940318746
Type: single nucleotide variant
Location: chr22:37024253 (GRCh38)
Gene constraint: LOEUF 1.501 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.74 · 2 PDB
Residue 13 UniProt numbering: an α-helix

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.Ala39Val Uncertain significance ★ ⚠ same type
MPST p.Ala45Ser Uncertain significance ★ ⚠ same type
MPST p.Ala77Val Uncertain significance ★ ⚠ same type
MPST p.Arg153Ser 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-ala33val (accessed [today's date]).

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