Is PTPRB p.Ser145Arg (c.435C>A) pathogenic?

PTPRB p.Ser145Arg (c.435C>A) is classified Uncertain significance in PTPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). Very rare (popmax 0.00167%, amr).

How common is PTPRB p.Ser145Arg (c.435C>A) in the general population?

PTPRB p.Ser145Arg (c.435C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

PTPRB p.Ser145Arg

c.435C>A · rs200607526 · VCV2375676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -3.2, phastCons 0.84
Regional constraint	o/e 0.94	unconstrained · MANE · 66 kb · p 0.021 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,908 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00638% 103/1,613,326 alleles · very rare exomes 92/1,461,212 · genomes 11/152,114 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.267%	374
Remaining individualsnot grpmax-eligible	0.016%	6,244
Admixed Americangrpmax	0.00167%	59,908
European (non-Finnish)	0.0011%	90,740

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PTPRB
Protein: p.Ser145Arg
Coding: c.435C>A
MANE Select: NM_001109754
dbSNP: rs200607526
Type: single nucleotide variant
Location: chr12:70635687 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 14 PDB
Residue 145: the fibronectin type-iii 2 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-ser145arg (accessed [today's date]).

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