Is PTPRA p.Asp2Val (c.5A>T) pathogenic?

PTPRA p.Asp2Val (c.5A>T) is classified Uncertain significance in PTPRA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.1619); Ultra-rare (popmax 0.0988%, nfe).

How common is PTPRA p.Asp2Val (c.5A>T) in the general population?

PTPRA p.Asp2Val (c.5A>T) is ultra-rare (popmax 0.0988%, nfe) (gnomAD).

What do computational predictors say about PTPRA p.Asp2Val (c.5A>T)?

AlphaMissense predicts likely benign (score 0.1619) — an in-silico prediction, not a clinical call.

PTPRA p.Asp2Val

c.5A>T · rs140259035 · VCV2361666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0988%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1619	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -7.32	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 6.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.65 · regional, not allelic
Overall
CADD	25.3	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 0.0988% European (non-Finnish) · 1,164/1,178,126 alleles

Filtering AF 0.0941% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0921%

Overall 0.0773% 1,244/1,610,146 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0988%	1,012
Finnishnot grpmax-eligible	0.0515%	1,940
Remaining individualsnot grpmax-eligible	0.0513%	1,949
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,929
African / African-American	0.00935%	10,694
Admixed American	0.00338%	29,599

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: PTPRA
Protein: p.Asp2Val
Coding: c.5A>T
MANE Select: NM_001385305
dbSNP: rs140259035
Type: single nucleotide variant
Location: chr20:2964282 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.51 · 1 PDB

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

Similar variants

VPS16 p.Arg587Ter Pathogenic/Likely pathogenic ★★ same type
VPS16 p.Arg643His Uncertain significance ★★ ⚠ same type
VPS16 p.Gly707Ser Uncertain significance ★★ ⚠ same type
VPS16 p.Leu651Arg Uncertain significance ★★ ⚠ same type
VPS16 p.Leu705Val Uncertain significance ★★ ⚠ same type
PTPRA p.Ala154= Benign ★★ same type
VPS16 c.1818+22G>A Benign ★★ same type
VPS16 c.2271+148G>A Benign ★★ 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/ptpra-p-asp2val (accessed [today's date]).

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