Is RANBP2 p.Ser587= (c.1761C>T) pathogenic?

RANBP2 p.Ser587= (c.1761C>T) is classified Likely benign in RANBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). Ultra-rare (popmax 0.0335%, eas); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Ser587= (c.1761C>T)?

RANBP2 p.Ser587= (c.1761C>T) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Ser587= (c.1761C>T) in the general population?

RANBP2 p.Ser587= (c.1761C>T) is ultra-rare (popmax 0.0335%, eas) (gnomAD).

How is Familial acute necrotizing encephalopathy inherited?

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

RANBP2 p.Ser587=

c.1761C>T · rs199659469 · VCV1159145

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, eas)

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 -0.83	GERP -1.2
Overall
CADD	7.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% East Asian · 15/44,724 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00435% 70/1,607,940 alleles · ultra-rare exomes 62/1,455,928 · genomes 8/152,012 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0335%	2,982
Remaining individualsnot grpmax-eligible	0.00805%	12,415
European (non-Finnish)	0.00407%	24,552
South Asian	0.00222%	45,100

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.Ser587=
Coding: c.1761C>T
MANE Select: NM_006267
dbSNP: rs199659469
Type: single nucleotide variant
Location: chr2:108753003 (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.Ser587Arg Uncertain significance ★ ⚠ same residue
SH3RF3 p.Pro587Gln 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-ser587 (accessed [today's date]).

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