GRB7 p.His161=
c.483C>T · rs139030455 · VCV784355
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.713%, 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 -7.4 | GERP -5 |
| Overall | ||
| CADD | 3.792 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.713%
African / African-American · 535/75,056 alleles
Filtering AF
0.663%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.643%
Overall
0.0374%
603/1,614,130 alleles · rare
exomes 304/1,461,828 · genomes 299/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.713% | 140 |
| Middle Eastern | 0.066% | 1,516 |
| Admixed American | 0.0483% | 2,069 |
| Remaining individualsnot grpmax-eligible | 0.0448% | 2,232 |
| South Asian | 0.0022% | 45,542 |
| European (non-Finnish) | 0.000424% | 236,004 |
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
- GRB7
- Protein
- p.His161=
- Coding
- c.483C>T
- MANE Select
- NM_005310
- dbSNP
- rs139030455
- Type
- single nucleotide variant
- Location
- chr17:39743199 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.04 · 14 PDB
- Residue 161
- the ras-associating domain; a β-strand
Similar variants
- GRB7 c.1210-4A>G Benign ★★ same type
- GRB7 c.307-4G>A Benign ★★ same type
- GRB7 p.Pro362Leu Benign ★★ same type
- GRB7 p.Thr419Lys Benign ★★ same type
- GRB7 c.-17T>C Uncertain significance ★ same type
- GRB7 c.-2C>A Uncertain significance ★ same type
- GRB7 c.-45G>A Uncertain significance ★ same type
- GRB7 c.-50G>A 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/grb7-p-his161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown