Is PTEN p.Phe90Ser (c.269T>C) pathogenic?

PTEN p.Phe90Ser (c.269T>C) is classified Pathogenic/Likely pathogenic in PTEN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.9992); Very rare (popmax 0.00134%, afr); Associated with PTEN-related disorder.

What condition is associated with PTEN p.Phe90Ser (c.269T>C)?

PTEN p.Phe90Ser (c.269T>C) is associated with PTEN-related disorder, intellectual disability, Cowden syndrome 1 (ClinVar).

How common is PTEN p.Phe90Ser (c.269T>C) in the general population?

PTEN p.Phe90Ser (c.269T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PTEN p.Phe90Ser (c.269T>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

PTEN p.Phe90Ser

c.269T>C · rs1859965098 · VCV976246

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PTEN-related disorder

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic ✓ concordant with ClinVar · top 8% in PTEN
REVEL	0.984	strongly pathogenic-leaning
SaProt	LLR -13.91	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 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00134% African / African-American · 1/74,876 alleles

Overall 0.000657% 1/152,148 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
Protein: p.Phe90Ser
Coding: c.269T>C
MANE Select: NM_000314
dbSNP: rs1859965098
Type: single nucleotide variant
Location: chr10:87933028 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 90: a β-strand; 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

PTEN-related disorder

Also linked: intellectual disability Cowden syndrome 1 PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Phe90fs Pathogenic ★★ same residue
PTEN p.Phe90Leu Likely pathogenic ★ same residue
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

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-phe90ser (accessed [today's date]).

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