Is RANBP2 p.Ser850= (c.2550A>G) pathogenic?

RANBP2 p.Ser850= (c.2550A>G) is classified Benign in RANBP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Common (popmax 69.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Ser850= (c.2550A>G)?

RANBP2 p.Ser850= (c.2550A>G) is associated with familial acute necrotizing encephalopathy (ClinVar).

How is Familial acute necrotizing encephalopathy inherited?

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

RANBP2 p.Ser850=

Q: How common is RANBP2 p.Ser850= (c.2550A>G) in the general population?

RANBP2 p.Ser850= (c.2550A>G) is common (popmax 69.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2550A>G · rs826549 · VCV380029

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 69.6%, afr) — too common for a highly-penetrant pathogenic allele

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 1.4	GERP -2.4, phastCons 0.99
Overall
CADD	6.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 69.6% African / African-American · 51,355/73,814 alleles

Filtering AF 69.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 68.9%

Overall 25.7% 413,717/1,606,792 alleles · common exomes 360,529/1,456,270 · genomes 53,188/150,522 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	69.6%	1
South Asian	32.9%	3
Middle Eastern	28.8%	3
Amishnot grpmax-eligible	26.9%	4
Remaining individualsnot grpmax-eligible	26.9%	4
Ashkenazi Jewishnot grpmax-eligible	24.6%	4
European (non-Finnish)	23.8%	4
Finnishnot grpmax-eligible	19%	5
Admixed American	18.4%	5
East Asian	9.38%	11

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.Ser850=
Coding: c.2550A>G
MANE Select: NM_006267
dbSNP: rs826549
Type: single nucleotide variant
Location: chr2:108758496 (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.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-ser850 (accessed [today's date]).

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