Is PTPRE p.Pro330Ala (c.988C>G) pathogenic?

PTPRE p.Pro330Ala (c.988C>G) is classified Uncertain significance in PTPRE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely benign (0.2192); Very rare (popmax 0.000339%, nfe).

How common is PTPRE p.Pro330Ala (c.988C>G) in the general population?

PTPRE p.Pro330Ala (c.988C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about PTPRE p.Pro330Ala (c.988C>G)?

AlphaMissense predicts likely benign (score 0.2192) — an in-silico prediction, not a clinical call.

PTPRE p.Pro330Ala

c.988C>G · VCV3428009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2192	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -3.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 35 kb · p 5.4e-11 · regional, not allelic
Overall
CADD	21.6	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 0.000339% European (non-Finnish) · 4/1,179,696 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,654 alleles · very rare exomes 4/1,461,314 · genomes 0/152,340 · 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.Pro330Ala
Coding: c.988C>G
MANE Select: NM_006504
Type: single nucleotide variant
Location: chr10:128068267 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.42 · 4 PDB
Residue 330: 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.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-pro330ala (accessed [today's date]).

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