Is RANBP2 p.Ala771= (c.2313A>G) pathogenic?

RANBP2 p.Ala771= (c.2313A>G) is classified Likely benign in RANBP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-30). Rare (popmax 0.215%, eas); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Ala771= (c.2313A>G)?

RANBP2 p.Ala771= (c.2313A>G) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Ala771= (c.2313A>G) in the general population?

RANBP2 p.Ala771= (c.2313A>G) is rare (popmax 0.215%, 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.Ala771=

c.2313A>G · rs76482726 · VCV1084120

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.215%, 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 2.5	GERP -2.1, phastCons 1
Overall
CADD	6.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% East Asian · 92/42,726 alleles

Filtering AF 0.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.0108% 173/1,607,094 alleles · rare exomes 169/1,454,868 · genomes 4/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.215%	464
Middle Eastern	0.0452%	2,210
Remaining individualsnot grpmax-eligible	0.0308%	3,251
African / African-American	0.0134%	7,454
Admixed American	0.00838%	11,936
European (non-Finnish)	0.00348%	28,748
South Asian	0.0033%	30,285
Finnishnot grpmax-eligible	0.00156%	63,960

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.Ala771=
Coding: c.2313A>G
MANE Select: NM_006267
dbSNP: rs76482726
Type: single nucleotide variant
Location: chr2:108755015 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)
Residue 771: the 'disordered' region

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

SH3RF3 p.Gly771Ser 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-ala771 (accessed [today's date]).

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