LYN p.Pro146=
c.438A>C · rs143618927 · VCV2746051
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.124%, 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 -0.72 | GERP -3.7 |
| Overall | ||
| CADD | 0.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.124%
African / African-American · 93/75,076 alleles
Filtering AF
0.103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.096%
Overall
0.00607%
98/1,614,178 alleles · rare
exomes 46/1,461,788 · genomes 52/152,390 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.124% | 807 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,834 |
| Admixed American | 0.00167% | 60,036 |
| Finnishnot grpmax-eligible | 0.00156% | 64,050 |
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.Pro146=
- Coding
- c.438A>C
- MANE Select
- NM_002350
- dbSNP
- rs143618927
- Type
- single nucleotide variant
- Location
- chr8:55950735 (GRCh38)
- Gene constraint
- LOEUF 0.282 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.44 · 6 PDB
- Residue 146
- the sh2 domain
Similar variants
- 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
- LYN p.Val45Ile 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-pro146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown