Is PTPRE p.Ala328Ser (c.982G>T) pathogenic?

PTPRE p.Ala328Ser (c.982G>T) is classified Uncertain significance in PTPRE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.0778); Ultra-rare (popmax 0.0117%, amr).

How common is PTPRE p.Ala328Ser (c.982G>T) in the general population?

PTPRE p.Ala328Ser (c.982G>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about PTPRE p.Ala328Ser (c.982G>T)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

PTPRE p.Ala328Ser

c.982G>T · VCV3940718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 35 kb · p 5.4e-11 · regional, not allelic
Overall
CADD	18.13	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 0.0117% Admixed American · 7/60,012 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000434% 7/1,613,948 alleles · ultra-rare exomes 7/1,461,616 · genomes 0/152,332 · 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: PTPRE
Protein: p.Ala328Ser
Coding: c.982G>T
MANE Select: NM_006504
Type: single nucleotide variant
Location: chr10:128068261 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.42 · 4 PDB
Residue 328: the tyrosine-protein phosphatase 1 domain

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.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
PTPRE p.Arg21Gly 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-ala328ser (accessed [today's date]).

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