RET p.Leu40=
c.120G>A · VCV3788292
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hereditary neoplastic 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 -0.39 | GERP -3.4, phastCons 0.005 |
| Overall | ||
| CADD | 4.885 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- RET
- Protein
- p.Leu40=
- Coding
- c.120G>A
- MANE Select
- NM_020975
- Type
- single nucleotide variant
- Location
- chr10:43100505 (GRCh38)
- Gene constraint
- LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.27 · 34 PDB
- Residue 40
- a β-strand; a UniProt-annotated variant site (in hscr1); the 'cadherin-like region 1 (cld1)' region
Similar variants
- RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RET p.Arg873Trp Likely pathogenic ★★ same condition
- RET p.Asp631Tyr Pathogenic ★★ ⚠ same condition
- RET p.Cys609Arg Pathogenic ★★ same condition
- RET p.Cys609Gly Pathogenic ★★ same condition
- RET p.Cys609Phe Pathogenic ★★ same condition
- RET p.Cys609Ser Pathogenic ★★ same condition
- RET p.Cys609Trp Pathogenic/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/ret-p-leu40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown