Is GMPPA p.Val391= (c.1173C>T) pathogenic?

GMPPA p.Val391= (c.1173C>T) is classified Likely benign in GMPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-22). Very rare (popmax 0.00834%, amr); Associated with alacrima, achalasia, and intellectual disability syndrome.

What condition is associated with GMPPA p.Val391= (c.1173C>T)?

GMPPA p.Val391= (c.1173C>T) is associated with alacrima, achalasia, and intellectual disability syndrome (ClinVar).

How common is GMPPA p.Val391= (c.1173C>T) in the general population?

GMPPA p.Val391= (c.1173C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

GMPPA p.Val391=

c.1173C>T · rs768293772 · VCV2417086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00834%, 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 1.1	GERP -0.2, phastCons 1
Overall
CADD	11.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,940 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000313% 5/1,595,034 alleles · very rare exomes 4/1,442,942 · genomes 1/152,092 · 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.Val391=
Coding: c.1173C>T
MANE Select: NM_013335
dbSNP: rs768293772
Type: single nucleotide variant
Location: chr2:219506708 (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-val391 (accessed [today's date]).

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