Is PTEN p.Asp92Ala (c.275A>C) pathogenic?

PTEN p.Asp92Ala (c.275A>C) is classified Pathogenic/Likely pathogenic in PTEN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-27). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Asp92Ala (c.275A>C)?

PTEN p.Asp92Ala (c.275A>C) is associated with hereditary neoplastic syndrome, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Asp92Ala (c.275A>C) in the general population?

PTEN p.Asp92Ala (c.275A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.Asp92Ala (c.275A>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

PTEN p.Asp92Ala

c.275A>C · rs1114167623 · VCV428196

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 8% in PTEN
REVEL	0.989	strongly pathogenic-leaning
SaProt	LLR -15.43	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 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

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.Asp92Ala
Coding: c.275A>C
MANE Select: NM_000314
dbSNP: rs1114167623
Type: single nucleotide variant
Location: chr10:87933034 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 92: the phosphatase tensin-type domain; a UniProt-annotated variant site (in mcephas)

Full PTEN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Asp92Glu Likely pathogenic ★★★ same residue
PTEN p.Asp92Gly Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Asp92Tyr Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Asp92Val Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Asp92_His93insTer Pathogenic ★★ same residue
PTEN p.Asp92Asn Likely pathogenic ★★ same residue
PTEN p.Asp92= Benign ★ same residue
PTEN c.1026+1G>A 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-p-asp92ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown