Is PTPRO p.Asp36= (c.108T>C) pathogenic?

PTPRO p.Asp36= (c.108T>C) is classified Benign/Likely benign in PTPRO (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.39%, nfe).

How common is PTPRO p.Asp36= (c.108T>C) in the general population?

PTPRO p.Asp36= (c.108T>C) is low-frequency (popmax 3.39%, nfe) (gnomAD).

PTPRO p.Asp36=

c.108T>C · rs17762440 · VCV1234355

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.39%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.2
Overall
CADD	4.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.39% European (non-Finnish) · 39,940/1,179,506 alleles

Filtering AF 3.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.35%

Overall 2.92% 47,164/1,613,578 alleles · low-frequency exomes 43,393/1,461,310 · genomes 3,771/152,268 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	15.2%	7
Finnishnot grpmax-eligible	5.23%	19
European (non-Finnish)grpmax	3.39%	30
Remaining individualsnot grpmax-eligible	2.65%	38
Admixed American	1.33%	75
Ashkenazi Jewishnot grpmax-eligible	1.06%	95
Middle Eastern	0.676%	148
South Asian	0.597%	167
African / African-American	0.505%	198
East Asian	0.00669%	14,958

Amish 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.Asp36=
Coding: c.108T>C
MANE Select: NM_030667
dbSNP: rs17762440
Type: single nucleotide variant
Location: chr12:15484006 (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.Asp36Asn Uncertain significance ★ ⚠ same residue
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

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-asp36 (accessed [today's date]).

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