Is PTPRO p.Tyr992= (c.2976C>T) pathogenic?

PTPRO p.Tyr992= (c.2976C>T) is classified Likely benign in PTPRO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). Very rare (popmax 0.00212%, nfe).

How common is PTPRO p.Tyr992= (c.2976C>T) in the general population?

PTPRO p.Tyr992= (c.2976C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

PTPRO p.Tyr992=

c.2976C>T · rs769224134 · VCV1983916

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.27	GERP -3.3, phastCons 0.99
Overall
CADD	6.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,400 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.0018% 29/1,612,260 alleles · very rare exomes 26/1,460,252 · genomes 3/152,008 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,220
Finnishnot grpmax-eligible	0.00317%	31,548
European (non-Finnish)grpmax	0.00212%	47,176

Remaining individuals 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: PTPRO
Protein: p.Tyr992=
Coding: c.2976C>T
MANE Select: NM_030667
dbSNP: rs769224134
Type: single nucleotide variant
Location: chr12:15580094 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 992: the tyrosine-protein phosphatase domain; a β-strand

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-tyr992 (accessed [today's date]).

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