Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.37%, afr)
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 -0.82 | GERP -3.4 |
| Overall | ||
| CADD | 7.735 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.37%
African / African-American · 2,531/75,000 alleles
Filtering AF
3.27%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.22%
Overall
0.192%
3,100/1,614,012 alleles · low-frequency
exomes 1,642/1,461,776 · genomes 1,458/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.37% | 30 |
| Middle Eastern | 0.629% | 159 |
| Admixed American | 0.33% | 303 |
| Remaining individualsnot grpmax-eligible | 0.301% | 332 |
| European (non-Finnish) | 0.0115% | 8,676 |
| South Asian | 0.00769% | 13,011 |
| East Asian | 0.00223% | 44,874 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
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
- GRB2
- Protein
- p.His79=
- Coding
- c.237C>T
- MANE Select
- NM_002086
- dbSNP
- rs2229610
- Type
- single nucleotide variant
- Location
- chr17:75325960 (GRCh38)
- Gene constraint
- LOEUF 0.216 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 88.89 · 58 PDB
- Residue 79
- the sh2 domain; a β-strand
Similar variants
- GRB2 p.Ala82Ser Uncertain significance ★ ⚠ same type
- GRB2 p.Arg207Cys Uncertain significance ★ same type
- GRB2 p.Arg215Trp Uncertain significance ★ ⚠ same type
- GRB2 p.Asn126Ser Uncertain significance ★ ⚠ same type
- GRB2 p.Asp133Asn Uncertain significance ★ ⚠ same type
- GRB2 p.Asp23Asn Uncertain significance ★ same type
- GRB2 p.Glu87Asp 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/grb2-p-his79 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown