Is RANBP2 p.Pro1020= (c.3060A>G) pathogenic?

RANBP2 p.Pro1020= (c.3060A>G) is classified Likely benign in RANBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). Very rare (popmax 0.005%, amr); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Pro1020= (c.3060A>G)?

RANBP2 p.Pro1020= (c.3060A>G) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Pro1020= (c.3060A>G) in the general population?

RANBP2 p.Pro1020= (c.3060A>G) is very rare (popmax 0.005%, amr) (gnomAD).

How is Familial acute necrotizing encephalopathy inherited?

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

RANBP2 p.Pro1020=

c.3060A>G · rs1312609974 · VCV794863

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

familial acute necrotizing encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 0.72, phastCons 1
Overall
CADD	5.159	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,974 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,614,032 alleles · very rare exomes 3/1,461,854 · genomes 2/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,991
European (non-Finnish)	0.000169%	590,009

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: RANBP2
Protein: p.Pro1020=
Coding: c.3060A>G
MANE Select: NM_006267
dbSNP: rs1312609974
Type: single nucleotide variant
Location: chr2:108763599 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)
Residue 1020: the '22 x 2 aa repeats of f-g' region

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.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
RANBP2 p.Arg1096Gln Uncertain significance ★★ ⚠ same condition
RANBP2 p.Arg1198Cys 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-pro1020 (accessed [today's date]).

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