Is RANBP2 p.Pro512= (c.1536G>A) pathogenic?

RANBP2 p.Pro512= (c.1536G>A) is classified Benign/Likely benign in RANBP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-01). Rare (popmax 0.63%, afr); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Pro512= (c.1536G>A)?

RANBP2 p.Pro512= (c.1536G>A) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Pro512= (c.1536G>A) in the general population?

RANBP2 p.Pro512= (c.1536G>A) is rare (popmax 0.63%, 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.Pro512=

c.1536G>A · rs370400502 · VCV1166292

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.63%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.7
Overall
CADD	0.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.63% African / African-American · 471/74,738 alleles

Filtering AF 0.583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.565%

Overall 0.0362% 583/1,610,794 alleles · rare exomes 320/1,458,920 · genomes 263/151,874 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.63%	159
East Asian	0.0691%	1,447
Admixed American	0.0534%	1,873
Remaining individualsnot grpmax-eligible	0.0466%	2,147
Middle Eastern	0.0451%	2,215
South Asian	0.0022%	45,484
European (non-Finnish)	0.00136%	73,698

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.Pro512=
Coding: c.1536G>A
MANE Select: NM_006267
dbSNP: rs370400502
Type: single nucleotide variant
Location: chr2:108751608 (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.Pro512Leu 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-pro512 (accessed [today's date]).

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