Is PTEN p.Asp22= (c.66C>T) pathogenic?

PTEN p.Asp22= (c.66C>T) is classified Likely benign in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-16). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Asp22= (c.66C>T)?

PTEN p.Asp22= (c.66C>T) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Asp22= (c.66C>T) in the general population?

PTEN p.Asp22= (c.66C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

PTEN p.Asp22=

c.66C>T · rs786201335 · VCV184205

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 6	GERP 1.9, phastCons 1
Overall
CADD	13.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,106 alleles · very rare exomes 5/1,461,752 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	0.000339%	294,984

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.Asp22=
Coding: c.66C>T
MANE Select: NM_000314
dbSNP: rs786201335
Type: single nucleotide variant
Location: chr10:87864535 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 22: a turn; the phosphatase tensin-type domain

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.Asp22His Likely pathogenic ★★★ same residue
PTEN p.Asp22Tyr Likely pathogenic ★★★ same residue
PTEN p.Asp22Glu Uncertain significance ★★ ⚠ same residue
PTEN p.Asp22Val Likely pathogenic ★ same residue
PTEN p.Asp22Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Asp22_Leu23insTer Pathogenic ★ same residue
PTEN p.Asp22fs Likely pathogenic ★ 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-asp22 (accessed [today's date]).

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