Is MPST p.Arg302Cys (c.904C>T) pathogenic?

MPST p.Arg302Cys (c.904C>T) is classified Uncertain significance in MPST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: ambiguous (0.4806); Ultra-rare (popmax 0.0334%, mid).

How common is MPST p.Arg302Cys (c.904C>T) in the general population?

MPST p.Arg302Cys (c.904C>T) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

What do computational predictors say about MPST p.Arg302Cys (c.904C>T)?

AlphaMissense predicts ambiguous (score 0.4806) — an in-silico prediction, not a clinical call.

MPST p.Arg302Cys

c.904C>T · VCV3397757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, mid)

Computational evidence

Protein change
AlphaMissense	0.4806	ambiguous
REVEL	0.419	indeterminate
SaProt	LLR -12.81	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 9,674 bp · p 0.34 · regional, not allelic
Overall
CADD	32.0	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 R282C vs ClinVar R302C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% Middle Eastern · 2/5,990 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00167% 27/1,612,072 alleles · ultra-rare exomes 24/1,459,752 · genomes 3/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0334%	2,995
African / African-American	0.00666%	15,006
East Asian	0.00446%	22,416
Remaining individualsnot grpmax-eligible	0.0016%	62,398
European (non-Finnish)	0.00136%	73,692
South Asian	0.0011%	91,000

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.Arg302Cys
Coding: c.904C>T
MANE Select: NM_021126
Type: single nucleotide variant
Location: chr22:37029464 (GRCh38)
Gene constraint: LOEUF 1.501 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.74 · 2 PDB
Residue 282 UniProt numbering: the rhodanese 2 domain; an α-helix

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

Similar variants

MPST p.Arg302His Uncertain significance ★ ⚠ same residue
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

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-arg302cys (accessed [today's date]).

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