Is PTPRM p.Phe1069Leu (c.3207T>A) pathogenic?

PTPRM p.Phe1069Leu (c.3207T>A) is classified Uncertain significance in PTPRM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.981); Absent from gnomAD v4.1; Associated with PTPRM-related disorder.

What condition is associated with PTPRM p.Phe1069Leu (c.3207T>A)?

PTPRM p.Phe1069Leu (c.3207T>A) is associated with PTPRM-related disorder (ClinVar).

How common is PTPRM p.Phe1069Leu (c.3207T>A) in the general population?

PTPRM p.Phe1069Leu (c.3207T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRM p.Phe1069Leu (c.3207T>A)?

AlphaMissense predicts likely pathogenic (score 0.981) — an in-silico prediction, not a clinical call.

PTPRM p.Phe1069Leu

c.3207T>A · VCV3344243

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

PTPRM-related disorder

Computational evidence

Protein change
AlphaMissense	0.981	likely pathogenic
REVEL	0.391	indeterminate
SaProt	LLR -11.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.98	GERP -0.76, phastCons 0.004
Regional constraint	o/e 0.82	unconstrained · MANE · 336 kb · p 3.6e-11 · regional, not allelic
Overall
CADD	18.23	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F1056L vs ClinVar F1069L) — verify the residue.

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: PTPRM
Protein: p.Phe1069Leu
Coding: c.3207T>A
MANE Select: NM_001105244
Type: single nucleotide variant
Location: chr18:8376081 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.38 · 5 PDB
Residue 1056 UniProt numbering: the tyrosine-protein phosphatase 1 domain; a β-strand

Full PTPRM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PTPRM-related disorder

Similar variants

PTPRM c.1754-6C>T Likely benign same condition
PTPRM c.3462+9G>A Likely benign same condition
PTPRM c.4045-5C>T Benign same condition
PTPRM c.839-7C>G Likely benign same condition
PTPRM p.Ala198= Likely benign same condition
PTPRM p.Ala673= Likely benign same condition
PTPRM p.Asn439= Benign same condition
PTPRM p.Gln1350= Likely benign 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/ptprm-p-phe1069leu (accessed [today's date]).

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