RET p.Val945=
c.2835G>C · rs2538614759 · VCV1796636
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 4.5 | GERP -2.6, phastCons 1 |
| Overall | ||
| CADD | 7.015 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,034 alleles
Overall
6.2e-05%
1/1,614,160 alleles · very rare
exomes 1/1,461,818 · genomes 0/152,342 · joint denominator
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
- RET
- Protein
- p.Val945=
- Coding
- c.2835G>C
- MANE Select
- NM_020975
- dbSNP
- rs2538614759
- Type
- single nucleotide variant
- Location
- chr10:43123704 (GRCh38)
- Gene constraint
- LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.27 · 34 PDB
- Residue 945
- an α-helix; the protein kinase domain
Similar variants
- RET p.Val945Leu Uncertain significance ★★ ⚠ same residue
- RET p.Val945Met Uncertain significance ★★ same residue
- RET p.Val945Gly Uncertain significance ★ ⚠ same residue
- RET p.Val945Ala Uncertain significance ★★ ⚠ same residue
- 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
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-val945 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown