Is RANBP2 p.Pro985= (c.2955G>A) pathogenic?

RANBP2 p.Pro985= (c.2955G>A) is classified Benign in RANBP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). Low-frequency (popmax 3.29%, eas); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Pro985= (c.2955G>A)?

RANBP2 p.Pro985= (c.2955G>A) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Pro985= (c.2955G>A) in the general population?

RANBP2 p.Pro985= (c.2955G>A) is low-frequency (popmax 3.29%, 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.Pro985=

c.2955G>A · rs61748147 · VCV382463

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.29%, 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 0.59	GERP -3.7, phastCons 0.033
Overall
CADD	3.937	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.29% East Asian · 1,477/44,884 alleles

Filtering AF 3.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.09%

Overall 0.697% 11,256/1,614,010 alleles · low-frequency exomes 10,493/1,461,822 · genomes 763/152,188 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	3.29%	30
South Asian	2.02%	50
Remaining individualsnot grpmax-eligible	0.672%	149
European (non-Finnish)	0.587%	170
Middle Eastern	0.511%	196
Ashkenazi Jewishnot grpmax-eligible	0.5%	200
Admixed American	0.493%	203
African / African-American	0.112%	893
Finnishnot grpmax-eligible	0.0672%	1,488

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.Pro985=
Coding: c.2955G>A
MANE Select: NM_006267
dbSNP: rs61748147
Type: single nucleotide variant
Location: chr2:108763494 (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.Pro985Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RANBP2 p.Pro985Arg 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-pro985 (accessed [today's date]).

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