Is PTEN p.Ala79Ser (c.235G>T) pathogenic?

PTEN p.Ala79Ser (c.235G>T) is classified Conflicting classifications of pathogenicity in PTEN (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0668); Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Ala79Ser (c.235G>T)?

PTEN p.Ala79Ser (c.235G>T) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Ala79Ser (c.235G>T) in the general population?

PTEN p.Ala79Ser (c.235G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PTEN p.Ala79Ser (c.235G>T)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

PTEN p.Ala79Ser

c.235G>T · rs202004587 · VCV404155

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.488	indeterminate
SaProt	LLR -4.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	21.6	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 0.00167% Admixed American · 1/59,784 alleles

Overall 0.000187% 3/1,605,928 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,784
Remaining individualsnot grpmax-eligible	0.00161%	62,110
European (non-Finnish)	8.52e-05%	1,173,834

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.Ala79Ser
Coding: c.235G>T
MANE Select: NM_000314
dbSNP: rs202004587
Type: single nucleotide variant
Location: chr10:87931071 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 79: 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

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.Ala79Thr Benign ★★★ same residue
PTEN p.Ala79Asp Uncertain significance ★ ⚠ same residue
PTEN p.Ala79= Likely benign ★ same residue
PTEN p.Ala79fs 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

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-ala79ser (accessed [today's date]).

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