Is RANBP2 p.Ala994= (c.2982A>T) pathogenic?

RANBP2 p.Ala994= (c.2982A>T) is classified Benign in RANBP2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). Rare (popmax 0.791%, amr); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Ala994= (c.2982A>T)?

RANBP2 p.Ala994= (c.2982A>T) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Ala994= (c.2982A>T) in the general population?

RANBP2 p.Ala994= (c.2982A>T) is rare (popmax 0.791%, 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.Ala994=

c.2982A>T · rs61748148 · VCV380576

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.791%, 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 2.4	GERP 0.69, phastCons 1
Overall
CADD	6.525	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.791% Admixed American · 475/60,028 alleles

Filtering AF 0.733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.719%

Overall 0.607% 9,804/1,614,172 alleles · rare exomes 9,078/1,461,836 · genomes 726/152,336 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.791%	126
European (non-Finnish)	0.737%	136
Middle Eastern	0.627%	160
Remaining individualsnot grpmax-eligible	0.56%	179
Amishnot grpmax-eligible	0.219%	456
Finnishnot grpmax-eligible	0.119%	843
African / African-American	0.116%	863
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
South Asian	0.0582%	1,719
East Asian	0.00223%	44,884

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.Ala994=
Coding: c.2982A>T
MANE Select: NM_006267
dbSNP: rs61748148
Type: single nucleotide variant
Location: chr2:108763521 (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.Ala994Thr 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-ala994 (accessed [today's date]).

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