Is PTEN p.His272= (c.816C>T) pathogenic?

PTEN p.His272= (c.816C>T) is classified Benign/Likely benign in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-02-13). Ultra-rare (popmax 0.0174%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.His272= (c.816C>T)?

PTEN p.His272= (c.816C>T) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.His272= (c.816C>T) in the general population?

PTEN p.His272= (c.816C>T) is ultra-rare (popmax 0.0174%, mid) (gnomAD).

PTEN p.His272=

c.816C>T · rs876659761 · VCV232432

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, mid)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.042, phastCons 1
Overall
CADD	8.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% Middle Eastern · 1/5,738 alleles

Overall 0.000318% 5/1,570,302 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0174%	5,738
Finnishnot grpmax-eligible	0.00667%	14,983

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.His272=
Coding: c.816C>T
MANE Select: NM_000314
dbSNP: rs876659761
Type: single nucleotide variant
Location: chr10:87960908 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 272: a β-strand; the c2 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: Cowden syndrome 1 PTEN hamartoma tumor syndrome

Similar variants

PTEN p.His272Pro Likely pathogenic ★ same residue
PTEN p.His272Gln Uncertain significance ★ ⚠ same residue
PTEN p.His272fs 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

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-his272 (accessed [today's date]).

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