Is PTPRB p.Phe740Ser (c.2219T>C) pathogenic?

PTPRB p.Phe740Ser (c.2219T>C) is classified Uncertain significance in PTPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). Absent from gnomAD v4.1.

How common is PTPRB p.Phe740Ser (c.2219T>C) in the general population?

PTPRB p.Phe740Ser (c.2219T>C) is absent from gnomAD v4.1 (gnomAD).

PTPRB p.Phe740Ser

c.2219T>C · VCV3427960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.568	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 66 kb · p 0.021 · regional, not allelic
Overall
CADD	27.2	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: PTPRB
Protein: p.Phe740Ser
Coding: c.2219T>C
MANE Select: NM_001109754
Type: single nucleotide variant
Location: chr12:70587099 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 14 PDB
Residue 740: the fibronectin type-iii 9 domain

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

Similar variants

PTPRB c.3370+4A>G Benign ★★ same type
PTPRB p.Ala1520= Benign ★★ same type
PTPRB p.Leu1142= Benign ★★ same type
PTPRB p.Pro1816= Benign/Likely benign ★★ same type
PTPRB p.Thr1699= Benign ★★ same type
PTPRB p.Ala1027Ser Uncertain significance ★ same type
PTPRB p.Ala1088Thr Uncertain significance ★ same type
PTPRB p.Ala1117Val Uncertain significance ★ same type

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/ptprb-p-phe740ser (accessed [today's date]).

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