Is GMPPA p.Pro19Ser (c.55C>T) pathogenic?

GMPPA p.Pro19Ser (c.55C>T) is classified Uncertain significance in GMPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely pathogenic (0.9949); Very rare (popmax 0.0098%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GMPPA p.Pro19Ser (c.55C>T)?

GMPPA p.Pro19Ser (c.55C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GMPPA p.Pro19Ser (c.55C>T) in the general population?

GMPPA p.Pro19Ser (c.55C>T) is very rare (popmax 0.0098%, nfe) (gnomAD).

What do computational predictors say about GMPPA p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely pathogenic (score 0.9949) — an in-silico prediction, not a clinical call.

GMPPA p.Pro19Ser

c.55C>T · VCV3520851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0098%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9949	likely pathogenic
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -15.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 0.99, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 6,819 bp · p 0.00018 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0098% European (non-Finnish) · 115/1,173,572 alleles

Filtering AF 0.0083% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00778%

Overall 0.00736% 118/1,602,950 alleles · very rare exomes 114/1,450,828 · genomes 4/152,122 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0098%	10,205
East Asian	0.00224%	44,678
Admixed American	0.00172%	58,124
Remaining individualsnot grpmax-eligible	0.00161%	62,094

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: GMPPA
Protein: p.Pro19Ser
Coding: c.55C>T
MANE Select: NM_013335
Type: single nucleotide variant
Location: chr2:219500135 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/gmppa-p-pro19ser (accessed [today's date]).

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