Is GMPPA p.Ser187= (c.561T>C) pathogenic?

GMPPA p.Ser187= (c.561T>C) is classified Likely benign in GMPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-04). Very rare (popmax 0.005%, amr); Associated with alacrima, achalasia, and intellectual disability syndrome.

What condition is associated with GMPPA p.Ser187= (c.561T>C)?

GMPPA p.Ser187= (c.561T>C) is associated with alacrima, achalasia, and intellectual disability syndrome (ClinVar).

How common is GMPPA p.Ser187= (c.561T>C) in the general population?

GMPPA p.Ser187= (c.561T>C) is very rare (popmax 0.005%, amr) (gnomAD).

GMPPA p.Ser187=

c.561T>C · rs764088206 · VCV2973448

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

alacrima, achalasia, and intellectual disability syndrome

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.085	GERP -2.5, phastCons 0.57
Overall
CADD	8.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,020 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,032 alleles · very rare exomes 3/1,461,758 · genomes 0/152,274 · joint denominator

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.Ser187=
Coding: c.561T>C
MANE Select: NM_013335
dbSNP: rs764088206
Type: single nucleotide variant
Location: chr2:219504154 (GRCh38)

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

Disease context

alacrima, achalasia, and intellectual disability syndrome — 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-ser187 (accessed [today's date]).

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