LYN p.Ala450=
c.1350C>T · rs142291090 · VCV1169421
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.991%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.7 |
| Overall | ||
| CADD | 2.166 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.991%
Middle Eastern · 60/6,052 alleles
Filtering AF
0.791%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.718%
Overall
0.0453%
731/1,613,810 alleles · rare
exomes 664/1,461,588 · genomes 67/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.991% | 101 |
| Ashkenazi Jewishnot grpmax-eligible | 0.402% | 249 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| South Asian | 0.0505% | 1,979 |
| European (non-Finnish) | 0.0348% | 2,871 |
| African / African-American | 0.0347% | 2,885 |
| Admixed American | 0.0267% | 3,750 |
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
- LYN
- Protein
- p.Ala450=
- Coding
- c.1350C>T
- MANE Select
- NM_002350
- dbSNP
- rs142291090
- Type
- single nucleotide variant
- Location
- chr8:56009921 (GRCh38)
- Gene constraint
- LOEUF 0.282 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.44 · 6 PDB
- Residue 450
- the protein kinase domain; an α-helix
Similar variants
- LYN p.Ala450Gly Uncertain significance ★ ⚠ same residue
- LYN p.Ala150Thr Uncertain significance ★★ ⚠ same type
- LYN p.Ala70Thr Uncertain significance ★★ ⚠ same type
- LYN p.Arg360Trp Uncertain significance ★★ ⚠ same type
- LYN p.Glu47Asp Uncertain significance ★★ ⚠ same type
- LYN p.Ile227Val Uncertain significance ★★ ⚠ same type
- LYN p.Ser333Asn Uncertain significance ★★ same type
- LYN p.Thr30Ala 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/lyn-p-ala450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown