Is GET3 p.His323Arg (c.968A>G) pathogenic?

GET3 p.His323Arg (c.968A>G) is classified Uncertain significance in GET3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.1562); Absent from gnomAD v4.1.

How common is GET3 p.His323Arg (c.968A>G) in the general population?

GET3 p.His323Arg (c.968A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GET3 p.His323Arg (c.968A>G)?

AlphaMissense predicts likely benign (score 0.1562) — an in-silico prediction, not a clinical call.

GET3 p.His323Arg

c.968A>G · rs2512785615 · VCV2542218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1562 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1562	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 76 bp · p 0.29 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GET3
Protein: p.His323Arg
Coding: c.968A>G
MANE Select: NM_004317
dbSNP: rs2512785615
Type: single nucleotide variant
Location: chr19:12748025 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 79.69 · 4 PDB
Residue 323: a UniProt-annotated variant site (in cmd2h; when associated in cis with variant w-289)

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

Similar variants

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
GET3 p.Asp284Asn 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-his323arg (accessed [today's date]).

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