Is RANBP2 p.Pro628Ser (c.1882C>T) pathogenic?

RANBP2 p.Pro628Ser (c.1882C>T) is classified Uncertain significance in RANBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: ambiguous (0.4677); Absent from gnomAD v4.1; Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Pro628Ser (c.1882C>T)?

RANBP2 p.Pro628Ser (c.1882C>T) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Pro628Ser (c.1882C>T) in the general population?

RANBP2 p.Pro628Ser (c.1882C>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial acute necrotizing encephalopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RANBP2 p.Pro628Ser (c.1882C>T)?

AlphaMissense predicts ambiguous (score 0.4677) — an in-silico prediction, not a clinical call.

RANBP2 p.Pro628Ser

c.1882C>T · rs2149230486 · VCV2880913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4677 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial acute necrotizing encephalopathy

Computational evidence

Protein change
AlphaMissense	0.4677	ambiguous
REVEL	0.324	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 2,249 bp · p 1.6e-13 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RANBP2
Protein: p.Pro628Ser
Coding: c.1882C>T
MANE Select: NM_006267
dbSNP: rs2149230486
Type: single nucleotide variant
Location: chr2:108753124 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)

Full RANBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial acute necrotizing encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial acute necrotizing encephalopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

RANBP2 p.Pro628Ala Uncertain significance ★ same residue
RANBP2 p.Pro628Thr Uncertain significance ★ same residue
RANBP2 p.Thr585Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
RANBP2 c.406-2A>G Uncertain significance ★★ same condition
RANBP2 p.Ala2564Ser Uncertain significance ★★ ⚠ same condition
RANBP2 p.Ala3072Val Uncertain significance ★★ ⚠ same condition
RANBP2 p.Ala534Val Uncertain significance ★★ same condition
RANBP2 p.Ala836Val 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/ranbp2-p-pro628ser (accessed [today's date]).

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