Is SH3BP2 p.Gly26Val (c.77G>T) pathogenic?

SH3BP2 p.Gly26Val (c.77G>T) is classified Uncertain significance in SH3BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.7544); Absent from gnomAD v4.1; Associated with cherubism.

What condition is associated with SH3BP2 p.Gly26Val (c.77G>T)?

SH3BP2 p.Gly26Val (c.77G>T) is associated with cherubism (ClinVar).

How common is SH3BP2 p.Gly26Val (c.77G>T) in the general population?

SH3BP2 p.Gly26Val (c.77G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SH3BP2 p.Gly26Val (c.77G>T)?

AlphaMissense predicts likely pathogenic (score 0.7544) — an in-silico prediction, not a clinical call.

SH3BP2 p.Gly26Val

c.77G>T · VCV4718701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7544 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cherubism

Computational evidence

Protein change
AlphaMissense	0.7544	likely pathogenic
REVEL	0.553	indeterminate
SaProt	LLR -9.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 4,027 bp · p 0.085 · regional, not allelic
Overall
CADD	27.3	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: SH3BP2
Protein: p.Gly26Val
Coding: c.77G>T
MANE Select: NM_001122681
Type: single nucleotide variant
Location: chr4:2820694 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.04 · 2 PDB
Residue 26: the ph domain

Full SH3BP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cherubism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SH3BP2 p.Gly26= Likely benign ★★ same residue
SH3BP2 p.Arg415Gln Pathogenic ★★ ⚠ same condition
SH3BP2 p.Gly420Arg Pathogenic ★★ ⚠ same condition
SH3BP2 p.Pro418Arg Pathogenic ★★ ⚠ same condition
SH3BP2 p.Pro418His Pathogenic/Likely pathogenic ★★ ⚠ same condition
SH3BP2 p.Pro418Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
SH3BP2 p.Pro418Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SH3BP2 p.Ala155Thr 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/sh3bp2-p-gly26val (accessed [today's date]).

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