PTEN c.253+7A>G
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 8.57e-05%, nfe)
Conditions
2
Cowden syndrome 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +7 | near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 0.5, phastCons 1 |
| Non-coding constraint | Z -0.86 | 1 kb window · o/e 1.07 · regional · uncalibrated |
| Overall | ||
| CADD | 14.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.57e-05%
European (non-Finnish) · 1/1,166,584 alleles
Overall
6.91e-05%
1/1,446,536 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
- PTEN
- Coding
- c.253+7A>G
- MANE Select
- NM_000314
- dbSNP
- rs2132239067
- Type
- single nucleotide variant
- Location
- chr10:87931096 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
Similar variants
- PTEN c.1026+1G>A Pathogenic ★★★ same condition
- PTEN c.1027-1852A>G Likely pathogenic ★★★ same condition
- PTEN c.1027-1G>A Pathogenic ★★★ same condition
- PTEN c.165-1G>A Likely pathogenic ★★★ same condition
- PTEN c.165-1G>C Pathogenic ★★★ same condition
- PTEN c.209+4A>G Pathogenic ★★★ same condition
- PTEN c.209+5G>C Likely pathogenic ★★★ same condition
- PTEN c.492+1G>T 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/pten-c-253-plus-7a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown