Is PTPRO p.Val233Ile (c.697G>A) pathogenic?

PTPRO p.Val233Ile (c.697G>A) is classified Uncertain significance in PTPRO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0727); Very rare (popmax 0.00801%, afr).

How common is PTPRO p.Val233Ile (c.697G>A) in the general population?

PTPRO p.Val233Ile (c.697G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about PTPRO p.Val233Ile (c.697G>A)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

PTPRO p.Val233Ile

c.697G>A · rs752358724 · VCV2623404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -3.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.9, phastCons 0.52
Regional constraint	o/e 0.93	unconstrained · MANE · 258 kb · p 0.015 · regional, not allelic
Overall
CADD	13.55	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,872 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00124% 20/1,613,714 alleles · very rare exomes 15/1,461,662 · genomes 5/152,052 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,479
South Asian	0.00549%	18,212
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,476
Finnishnot grpmax-eligible	0.00156%	63,994
European (non-Finnish)	0.000509%	196,646

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: PTPRO
Protein: p.Val233Ile
Coding: c.697G>A
MANE Select: NM_030667
dbSNP: rs752358724
Type: single nucleotide variant
Location: chr12:15501655 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB

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

Similar variants

PTPRO p.Ala1086Val Uncertain significance ★★ ⚠ same type
PTPRO p.Ala591Thr Uncertain significance ★★ ⚠ same type
PTPRO p.Arg480Trp Uncertain significance ★★ same type
PTPRO p.Arg607Gln Uncertain significance ★★ ⚠ same type
PTPRO p.Asn569Asp Uncertain significance ★★ ⚠ same type
PTPRO p.Asp162Val Uncertain significance ★★ ⚠ same type
PTPRO p.Asp301His Uncertain significance ★★ ⚠ same type
PTPRO p.Asp799Gly 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/ptpro-p-val233ile (accessed [today's date]).

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