Is RANBP2 p.Pro1011= (c.3033G>A) pathogenic?

RANBP2 p.Pro1011= (c.3033G>A) is classified Benign/Likely benign in RANBP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-16). Low-frequency (popmax 1.61%, afr); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Pro1011= (c.3033G>A)?

RANBP2 p.Pro1011= (c.3033G>A) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Pro1011= (c.3033G>A) in the general population?

RANBP2 p.Pro1011= (c.3033G>A) is low-frequency (popmax 1.61%, afr) (gnomAD).

How is Familial acute necrotizing encephalopathy inherited?

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

RANBP2 p.Pro1011=

c.3033G>A · rs78215631 · VCV469445

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.61%, afr)

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 -0.2	GERP -3.7, phastCons 0.007
Overall
CADD	5.564	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.61% African / African-American · 1,206/75,002 alleles

Filtering AF 1.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5%

Overall 0.0849% 1,371/1,614,020 alleles · low-frequency exomes 696/1,461,840 · genomes 675/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.61%	62
Admixed American	0.117%	857
Remaining individualsnot grpmax-eligible	0.109%	919
Middle Eastern	0.066%	1,516
East Asian	0.00446%	22,435
South Asian	0.00329%	30,361
European (non-Finnish)	0.00153%	65,555

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.Pro1011=
Coding: c.3033G>A
MANE Select: NM_006267
dbSNP: rs78215631
Type: single nucleotide variant
Location: chr2:108763572 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)
Residue 1011: 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.Pro1011Leu 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
RANBP2 p.Arg1096Gln 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-pro1011 (accessed [today's date]).

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