Is PTEN p.Arg142= (c.424C>A) pathogenic?

PTEN p.Arg142= (c.424C>A) is classified Conflicting classifications of pathogenicity in PTEN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-08). Absent from gnomAD v4.1; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Arg142= (c.424C>A)?

PTEN p.Arg142= (c.424C>A) is associated with PTEN hamartoma tumor syndrome, Cowden syndrome 1 (ClinVar).

How common is PTEN p.Arg142= (c.424C>A) in the general population?

PTEN p.Arg142= (c.424C>A) is absent from gnomAD v4.1 (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PTEN p.Arg142=

c.424C>A · rs746152219 · VCV1213667

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PTEN hamartoma tumor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Pangolin	Δ0.22	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Overall
CADD	19.48	PHRED · no single calibrated threshold — expert panels disagree

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.Arg142=
Coding: c.424C>A
MANE Select: NM_000314
dbSNP: rs746152219
Type: single nucleotide variant
Location: chr10:87933183 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 142: an α-helix; 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 hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cowden syndrome 1

For PTEN hamartoma tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PTEN p.Arg142Trp Uncertain significance ★★★ ⚠ same residue
PTEN p.Arg142Pro Likely pathogenic ★★ same residue
PTEN p.Arg142Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Arg142Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Arg142fs 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

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-arg142 (accessed [today's date]).

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