Is PTPRO p.Pro804Ser (c.2410C>T) pathogenic?

PTPRO p.Pro804Ser (c.2410C>T) is classified Uncertain significance in PTPRO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.225); Very rare (popmax 8.48e-05%, nfe).

How common is PTPRO p.Pro804Ser (c.2410C>T) in the general population?

PTPRO p.Pro804Ser (c.2410C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PTPRO p.Pro804Ser (c.2410C>T)?

AlphaMissense predicts likely benign (score 0.225) — an in-silico prediction, not a clinical call.

PTPRO p.Pro804Ser

c.2410C>T · rs1467017091 · VCV2101861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.225 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.225	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 258 kb · p 0.015 · regional, not allelic
Overall
CADD	24.6	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 8.48e-05% European (non-Finnish) · 1/1,179,200 alleles

Overall 6.2e-05% 1/1,612,214 alleles · very rare exomes 0/1,460,488 · genomes 1/151,726 · 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: PTPRO
Protein: p.Pro804Ser
Coding: c.2410C>T
MANE Select: NM_030667
dbSNP: rs1467017091
Type: single nucleotide variant
Location: chr12:15549199 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 804: the fibronectin type-iii 8 domain

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-pro804ser (accessed [today's date]).

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