Is RPN2 p.Pro327= (c.981T>A) pathogenic?

RPN2 p.Pro327= (c.981T>A) is classified Likely benign in RPN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-25). Very rare (popmax 8.47e-05%, nfe); Associated with congenital disorder of glycosylation.

What condition is associated with RPN2 p.Pro327= (c.981T>A)?

RPN2 p.Pro327= (c.981T>A) is associated with congenital disorder of glycosylation (ClinVar).

How common is RPN2 p.Pro327= (c.981T>A) in the general population?

RPN2 p.Pro327= (c.981T>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

RPN2 p.Pro327=

c.981T>A · rs2146608181 · VCV1091580

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -2.9
Overall
CADD	6.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,990 alleles

Overall 6.84e-05% 1/1,461,618 alleles · very rare

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: RPN2
Protein: p.Pro327=
Coding: c.981T>A
MANE Select: NM_002951
dbSNP: rs2146608181
Type: single nucleotide variant
Location: chr20:37210160 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 6 PDB

Full RPN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RPN2 p.Ala558Thr Uncertain significance ★★ ⚠ same condition
RPN2 p.Ala584Ser Uncertain significance ★★ ⚠ same condition
RPN2 p.Arg76Thr Uncertain significance ★★ ⚠ same condition
RPN2 p.Asn497Ser Uncertain significance ★★ ⚠ same condition
RPN2 p.Asn543Ser Uncertain significance ★★ ⚠ same condition
RPN2 p.Asp85Gly Uncertain significance ★★ ⚠ same condition
RPN2 p.Glu182Asp Uncertain significance ★★ ⚠ same condition
RPN2 p.His439Arg Uncertain significance ★★ ⚠ same condition

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/rpn2-p-pro327 (accessed [today's date]).

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