Is PTPRJ p.Ser347Pro (c.1039T>C) pathogenic?

PTPRJ p.Ser347Pro (c.1039T>C) is classified Likely benign in PTPRJ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0817); Very rare (popmax 0.008%, afr).

How common is PTPRJ p.Ser347Pro (c.1039T>C) in the general population?

PTPRJ p.Ser347Pro (c.1039T>C) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about PTPRJ p.Ser347Pro (c.1039T>C)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

PTPRJ p.Ser347Pro

c.1039T>C · VCV4147918

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.023	GERP -3.8, phastCons 0.087
Regional constraint	o/e 0.95	unconstrained · MANE · 186 kb · p 0.055 · regional, not allelic
Overall
CADD	4.738	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 0.008% African / African-American · 6/74,994 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000372% 6/1,614,022 alleles · very rare exomes 1/1,461,886 · genomes 5/152,136 · joint denominator

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: PTPRJ
Protein: p.Ser347Pro
Coding: c.1039T>C
MANE Select: NM_002843
Type: single nucleotide variant
Location: chr11:48125132 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.58 · 5 PDB
Residue 347: the fibronectin type-iii 3 domain; a β-strand

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

Similar variants

PTPRJ p.Gln356Arg Uncertain significance ★★ ⚠ same type
PTPRJ p.Gly773Asp Uncertain significance ★★ ⚠ same type
PTPRJ c.3042-6A>G Benign ★★ same type
PTPRJ p.Ala293Thr Benign ★★ same type
PTPRJ p.Arg418His Likely benign ★★ same type
PTPRJ p.Asn192Ser Benign ★★ same type
PTPRJ p.His451Arg Benign ★★ same type
PTPRJ p.Ile1235Thr Benign ★★ 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/ptprj-p-ser347pro (accessed [today's date]).

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