Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 14 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.31%, afr)
Conditions
4
Noonan syndrome and Noonan-related syndrome
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 0.33 | GERP 0.69, phastCons 1 |
| Overall | ||
| CADD | 10.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.31%
African / African-American · 1,736/75,034 alleles
Filtering AF
2.22%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.19%
Overall
0.281%
4,541/1,614,036 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.31% | 43 |
| South Asian | 1.56% | 64 |
| Middle Eastern | 0.396% | 252 |
| Remaining individualsnot grpmax-eligible | 0.381% | 263 |
| Admixed American | 0.192% | 522 |
| European (non-Finnish) | 0.0839% | 1,192 |
| Finnishnot grpmax-eligible | 0.0187% | 5,336 |
| East Asian | 0.00223% | 44,860 |
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
- CBL
- Protein
- p.Ser171=
- Coding
- c.513T>C
- MANE Select
- NM_005188
- dbSNP
- rs2227987
- Type
- single nucleotide variant
- Location
- chr11:119271804 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
- Residue 171
- the cbl-ptb domain; the 'sufficient for interaction with ephb1' region; the '4h' region; an α-helix
Similar variants
- CBL p.Ser171Gly Uncertain significance ★★ ⚠ same residue
- CBL c.1096-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CBL c.1096-1G>T Pathogenic ★★ same condition
- CBL c.1096-2A>T Pathogenic ★★ same condition
- CBL c.1228-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Arg420Leu Likely pathogenic ★★ same condition
- CBL p.Gln367Arg Likely pathogenic ★★ 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/cbl-p-ser171 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown