Is PTEN p.Phe241= (c.723T>C) pathogenic?

PTEN p.Phe241= (c.723T>C) is classified Benign/Likely benign in PTEN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-10-13). Ultra-rare (popmax 0.0178%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Phe241= (c.723T>C)?

PTEN p.Phe241= (c.723T>C) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Phe241= (c.723T>C) in the general population?

PTEN p.Phe241= (c.723T>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

PTEN p.Phe241=

c.723T>C · rs17849090 · VCV215733

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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 0.41	GERP -4.6, phastCons 1
Overall
CADD	12.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,866 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000616% 9/1,461,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,608
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Phe241=
Coding: c.723T>C
MANE Select: NM_000314
dbSNP: rs17849090
Type: single nucleotide variant
Location: chr10:87957941 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 241: 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.Phe241Ser Likely pathogenic ★★★ same residue
PTEN p.Phe241Ile Uncertain significance ★★ ⚠ same residue
PTEN p.Phe241Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Phe241_Asn262del Likely pathogenic ★ same residue
PTEN p.Phe241del Likely pathogenic ★ same residue
PTEN p.Phe241fs Pathogenic ★ same residue
PTEN p.Phe241Val Uncertain significance ★ ⚠ 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-phe241 (accessed [today's date]).

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