Is RANBP2 p.Pro611= (c.1833A>G) pathogenic?

RANBP2 p.Pro611= (c.1833A>G) is classified Likely benign in RANBP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-10). Very rare (popmax 0.00335%, amr); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Pro611= (c.1833A>G)?

RANBP2 p.Pro611= (c.1833A>G) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Pro611= (c.1833A>G) in the general population?

RANBP2 p.Pro611= (c.1833A>G) is very rare (popmax 0.00335%, 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.Pro611=

c.1833A>G · rs1558904916 · VCV1082531

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00335%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -1.1
Overall
CADD	6.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00335% Admixed American · 2/59,674 alleles

Filtering AF 0.000556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000683% 11/1,609,708 alleles · very rare exomes 9/1,457,674 · genomes 2/152,034 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,837
Remaining individualsnot grpmax-eligible	0.00322%	31,090
European (non-Finnish)	0.000594%	168,394

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.Pro611=
Coding: c.1833A>G
MANE Select: NM_006267
dbSNP: rs1558904916
Type: single nucleotide variant
Location: chr2:108753075 (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.Pro611Leu Uncertain significance ★ ⚠ same residue
RANBP2 p.Pro611Ser 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-pro611 (accessed [today's date]).

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