RET p.Ala883=
c.2649T>A · rs2132960541 · VCV1087630
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
2
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 -9.1 | GERP -4.3 |
| Overall | ||
| CADD | 1.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,010 alleles
Overall
6.84e-05%
1/1,461,708 alleles · very rare
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.Ala883=
- Coding
- c.2649T>A
- MANE Select
- NM_020975
- dbSNP
- rs2132960541
- Type
- single nucleotide variant
- Location
- chr10:43120122 (GRCh38)
- Gene constraint
- LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.27 · 34 PDB
- Residue 883
- a UniProt-annotated variant site (in men2b; somatic mutation in sporadic medullary thyroid carcinoma; requires 2 nucleotide substitutions); a β-strand; the protein kinase domain
Similar variants
- RET p.Ala883Asp Uncertain significance ★★ ⚠ same residue
- RET p.Ala883Pro Uncertain significance ★★ ⚠ same residue
- RET p.Ala883Thr Uncertain significance ★★ ⚠ same residue
- RET p.Ala883Val Uncertain significance ★ ⚠ same residue
- RET p.Ala883Phe Pathogenic/Likely pathogenic ★★ same residue
- RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RET c.1879+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RET p.Arg180Ter 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-ala883 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown