Is MPST p.Arg302His (c.905G>A) pathogenic?

MPST p.Arg302His (c.905G>A) is classified Uncertain significance in MPST (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.2778); Very rare (popmax 0.008%, afr).

How common is MPST p.Arg302His (c.905G>A) in the general population?

MPST p.Arg302His (c.905G>A) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about MPST p.Arg302His (c.905G>A)?

AlphaMissense predicts likely benign (score 0.2778) — an in-silico prediction, not a clinical call.

MPST p.Arg302His

c.905G>A · rs565373616 · VCV3203462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2778	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 9,674 bp · p 0.34 · regional, not allelic
Overall
CADD	31.0	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 R282H vs ClinVar R302H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/75,044 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00211% 34/1,612,150 alleles · very rare exomes 26/1,459,820 · genomes 8/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,507
Admixed American	0.00334%	29,982
Remaining individualsnot grpmax-eligible	0.0032%	31,203
South Asian	0.0022%	45,509
European (non-Finnish)	0.00187%	53,595

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.Arg302His
Coding: c.905G>A
MANE Select: NM_021126
dbSNP: rs565373616
Type: single nucleotide variant
Location: chr22:37029465 (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.Arg302Cys 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-arg302his (accessed [today's date]).

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