Is SH2B3 p.Pro344= (c.1032T>C) pathogenic?

SH2B3 p.Pro344= (c.1032T>C) is classified Likely benign in SH2B3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SH2B3 p.Pro344= (c.1032T>C)?

SH2B3 p.Pro344= (c.1032T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SH2B3 p.Pro344= (c.1032T>C) in the general population?

SH2B3 p.Pro344= (c.1032T>C) is absent from gnomAD v4.1 (gnomAD).

SH2B3 p.Pro344=

c.1032T>C · VCV3795225

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.61	GERP -0.41, phastCons 0.053
Overall
CADD	8.476	PHRED · no single calibrated threshold — expert panels disagree

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: SH2B3
Protein: p.Pro344=
Coding: c.1032T>C
MANE Select: NM_005475
Type: single nucleotide variant
Location: chr12:111447340 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.45
Residue 344: a UniProt-annotated variant site (found in a patient with isolated erythrocytosis; uncertain significance); the 'disordered' region

Full SH2B3 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

Similar variants

SH2B3 p.Pro344His Uncertain significance ★ ⚠ same residue
SH2B3 p.Pro344Leu Benign/Likely benign ★★ same residue
SH2B3 p.Ala161Val Uncertain significance ★★ ⚠ same condition
SH2B3 p.Ala174Thr Uncertain significance ★★ ⚠ same condition
SH2B3 p.Ala300Thr Uncertain significance ★★ ⚠ same condition
SH2B3 p.Arg221Met Uncertain significance ★★ ⚠ same condition
SH2B3 p.Arg226Trp Uncertain significance ★★ ⚠ same condition
SH2B3 p.Arg235Cys Uncertain significance ★★ ⚠ same condition

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/sh2b3-p-pro344 (accessed [today's date]).

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