Is PTPRO p.Val671Ala (c.2012T>C) pathogenic?

PTPRO p.Val671Ala (c.2012T>C) is classified Uncertain significance in PTPRO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). AlphaMissense: likely benign (0.1645); Absent from gnomAD v4.1.

How common is PTPRO p.Val671Ala (c.2012T>C) in the general population?

PTPRO p.Val671Ala (c.2012T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRO p.Val671Ala (c.2012T>C)?

AlphaMissense predicts likely benign (score 0.1645) — an in-silico prediction, not a clinical call.

PTPRO p.Val671Ala

c.2012T>C · rs2539990320 · VCV3149555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1645 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1645	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.91 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 258 kb · p 0.015 · regional, not allelic
Overall
CADD	22.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTPRO
Protein: p.Val671Ala
Coding: c.2012T>C
MANE Select: NM_030667
dbSNP: rs2539990320
Type: single nucleotide variant
Location: chr12:15524934 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 671: the fibronectin type-iii 7 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-val671ala (accessed [today's date]).

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