Is SH2B3 p.Arg149= (c.447C>T) pathogenic?

SH2B3 p.Arg149= (c.447C>T) is classified Likely benign in SH2B3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SH2B3 p.Arg149= (c.447C>T)?

SH2B3 p.Arg149= (c.447C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SH2B3 p.Arg149= (c.447C>T) in the general population?

SH2B3 p.Arg149= (c.447C>T) is absent from gnomAD v4.1 (gnomAD).

SH2B3 p.Arg149=

c.447C>T · VCV4630704

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,490,868)

Conditions

Inborn genetic diseases

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 -1	GERP -1.5, phastCons 0.003
Overall
CADD	5.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,490,868). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SH2B3
Protein: p.Arg149=
Coding: c.447C>T
MANE Select: NM_005475
Type: single nucleotide variant
Location: chr12:111418592 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.45

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.Arg149Cys Uncertain significance ★ ⚠ 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
SH2B3 p.Arg39Gln 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-arg149 (accessed [today's date]).

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