Is PTPRE p.Ser82Arg (c.246C>A) pathogenic?

PTPRE p.Ser82Arg (c.246C>A) is classified Uncertain significance in PTPRE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). AlphaMissense: ambiguous (0.3436); Ultra-rare (popmax 0.0496%, mid).

How common is PTPRE p.Ser82Arg (c.246C>A) in the general population?

PTPRE p.Ser82Arg (c.246C>A) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about PTPRE p.Ser82Arg (c.246C>A)?

AlphaMissense predicts ambiguous (score 0.3436) — an in-silico prediction, not a clinical call.

PTPRE p.Ser82Arg

c.246C>A · VCV3428010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3436 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3436	ambiguous
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -1.9
Regional constraint	o/e 0.77	unconstrained · MANE · 35 kb · p 5.4e-11 · regional, not allelic
Overall
CADD	13.62	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0496% Middle Eastern · 3/6,050 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.000872% 14/1,605,256 alleles · ultra-rare exomes 10/1,452,936 · genomes 4/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
Admixed American	0.01%	9,951
East Asian	0.00224%	44,590
European (non-Finnish)	0.000341%	293,212

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: PTPRE
Protein: p.Ser82Arg
Coding: c.246C>A
MANE Select: NM_006504
Type: single nucleotide variant
Location: chr10:128047800 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.42 · 4 PDB

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

Similar variants

PTPRE p.Ala129Thr Uncertain significance ★ ⚠ same type
PTPRE p.Ala289Val Uncertain significance ★ ⚠ same type
PTPRE p.Ala328Ser Uncertain significance ★ ⚠ same type
PTPRE p.Ala578Thr Uncertain significance ★ ⚠ same type
PTPRE p.Ala602Thr Uncertain significance ★ ⚠ same type
PTPRE p.Ala65Val Uncertain significance ★ ⚠ same type
PTPRE p.Ala66Thr Uncertain significance ★ ⚠ same type
PTPRE p.Arg125His 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/ptpre-p-ser82arg (accessed [today's date]).

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