Is MPST p.Ala19Ser (c.55G>T) pathogenic?

MPST p.Ala19Ser (c.55G>T) is classified Uncertain significance in MPST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). Very rare (popmax 0.00592%, eas).

How common is MPST p.Ala19Ser (c.55G>T) in the general population?

MPST p.Ala19Ser (c.55G>T) is very rare (popmax 0.00592%, eas) (gnomAD).

MPST p.Ala19Ser

c.55G>T · VCV3874259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00592%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -2.8
Regional constraint	o/e 1.04	unconstrained · MANE · 9,674 bp · p 0.34 · regional, not allelic
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00592% East Asian · 2/33,794 alleles

Filtering AF 0.00098% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000217% 3/1,379,646 alleles · very rare exomes 3/1,227,354 · genomes 0/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00592%	16,897
Remaining individualsnot grpmax-eligible	0.0019%	52,670

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.Ala19Ser
Coding: c.55G>T
MANE Select: NM_021126
Type: single nucleotide variant
Location: chr22:37024210 (GRCh38)
Gene constraint: LOEUF 1.501 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.74 · 2 PDB
Residue 19: 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.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
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-ala19ser (accessed [today's date]).

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