Is SH3BP2 p.Pro374= (c.1122C>T) pathogenic?

SH3BP2 p.Pro374= (c.1122C>T) is classified Benign/Likely benign in SH3BP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Rare (popmax 0.198%, eas); Associated with cherubism.

What condition is associated with SH3BP2 p.Pro374= (c.1122C>T)?

SH3BP2 p.Pro374= (c.1122C>T) is associated with cherubism (ClinVar).

How common is SH3BP2 p.Pro374= (c.1122C>T) in the general population?

SH3BP2 p.Pro374= (c.1122C>T) is rare (popmax 0.198%, eas) (gnomAD).

SH3BP2 p.Pro374=

c.1122C>T · rs149122170 · VCV454489

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.198%, eas)

Conditions

cherubism

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 -20	GERP -3.2
Overall
CADD	0.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% East Asian · 89/44,884 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.0182% 294/1,612,890 alleles · rare exomes 233/1,460,524 · genomes 61/152,366 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.198%	504
Middle Eastern	0.115%	866
Admixed American	0.103%	968
African / African-American	0.0493%	2,029
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.0143%	7,007
European (non-Finnish)	0.00551%	18,153
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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: SH3BP2
Protein: p.Pro374=
Coding: c.1122C>T
MANE Select: NM_001122681
dbSNP: rs149122170
Type: single nucleotide variant
Location: chr4:2830028 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.04 · 2 PDB
Residue 374: the 'disordered' region

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.Pro374Ser Uncertain significance ★ ⚠ 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-pro374 (accessed [today's date]).

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