RET p.Val25=
c.75G>A · VCV4863274
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.94 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.68 | gain · loss 0.07 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.5 | GERP -3.4, phastCons 0.019 |
| Overall | ||
| CADD | 17.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,044 alleles
Overall
6.2e-05%
1/1,612,776 alleles · very rare
exomes 1/1,461,416 · genomes 0/151,360 · 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.Val25=
- Coding
- c.75G>A
- MANE Select
- NM_020975
- Type
- single nucleotide variant
- Location
- chr10:43100460 (GRCh38)
- Gene constraint
- LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.27 · 34 PDB
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-val25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown