Is GET3 p.Pro344= (c.1032C>A) pathogenic?

GET3 p.Pro344= (c.1032C>A) is classified Likely benign in GET3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Very rare (popmax 8.54e-05%, nfe).

How common is GET3 p.Pro344= (c.1032C>A) in the general population?

GET3 p.Pro344= (c.1032C>A) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

GET3 p.Pro344=

c.1032C>A · VCV4281374

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -0.02, phastCons 0.003
Overall
CADD	7.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,170,468 alleles

Overall 6.25e-05% 1/1,599,966 alleles · very rare exomes 1/1,447,688 · genomes 0/152,278 · 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: GET3
Protein: p.Pro344=
Coding: c.1032C>A
MANE Select: NM_004317
Type: single nucleotide variant
Location: chr19:12748089 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 79.69 · 4 PDB
Residue 344: a UniProt-annotated variant site (in cmd2h; when associated in cis with variant w-289); an α-helix

Full GET3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GET3 p.Pro344Ser Uncertain significance ★ ⚠ same residue
GET3 p.Ala112Gly Uncertain significance ★ ⚠ same type
GET3 p.Ala112Val Uncertain significance ★ ⚠ same type
GET3 p.Ala82Thr Uncertain significance ★ ⚠ same type
GET3 p.Arg230His Uncertain significance ★ ⚠ same type
GET3 p.Arg35Cys Uncertain significance ★ ⚠ same type
GET3 p.Arg65Cys Uncertain significance ★ ⚠ same type
GET3 p.Arg65His 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/get3-p-pro344 (accessed [today's date]).

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