PTEN p.Asp24Asn
c.70G>A · rs786201995 · VCV185200
ClinGen expert panel — PTEN VCEP
Pathogenic for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):
PS2_VeryStrong PM2_Supporting PS3_Moderate PP2 PP3
Curation rationale (ClinGen, verbatim)
PTEN c.70G>A (p.Asp24Asn) meets criteria to be classified as Pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.2.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS2_VS: At least two proven OR one proven plus two assumed de novo observations in a patient with the disease and no family history. (internal laboratory contributors SCV001765320.4 and SCV005768039.2). PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = [-1.549791026] (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score > 0.7 (score of this variant = 0.753) PM2_P: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9997 | likely pathogenic ✓ concordant with ClinVar · top 8% in PTEN |
|---|---|---|
| REVEL | 0.753 | pathogenic-leaning |
| SaProt | LLR -12.55 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.27 | constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic |
| Overall | ||
| CADD | 28.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
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
- PTEN
- Protein
- p.Asp24Asn
- Coding
- c.70G>A
- MANE Select
- NM_000314
- dbSNP
- rs786201995
- Type
- single nucleotide variant
- Location
- chr10:87864539 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 24
- a β-strand; the phosphatase tensin-type domain
Disease context
PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hereditary neoplastic syndrome
For PTEN hamartoma tumor syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- PTEN p.Asp24His Pathogenic ★★★ same residue
- PTEN p.Asp24Gly Pathogenic/Likely pathogenic ★★ same residue
- PTEN p.Asp24Val Pathogenic/Likely pathogenic ★★ same residue
- PTEN p.Asp24= Benign/Likely benign ★★ same residue
- PTEN p.Asp24Ala Uncertain significance ★ ⚠ same residue
- PTEN p.Asp24Glu Uncertain significance ★ ⚠ same residue
- PTEN p.Asp24_Leu25insTer Likely pathogenic ★ same residue
- PTEN p.Asp24Tyr Pathogenic ★★ same residue
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-p-asp24asn (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown