Is RANBP2 p.Val875= (c.2625A>G) pathogenic?

RANBP2 p.Val875= (c.2625A>G) is classified Benign/Likely benign in RANBP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). Rare (popmax 0.889%, eas); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Val875= (c.2625A>G)?

RANBP2 p.Val875= (c.2625A>G) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Val875= (c.2625A>G) in the general population?

RANBP2 p.Val875= (c.2625A>G) is rare (popmax 0.889%, 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.Val875=

c.2625A>G · rs200515712 · VCV469443

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.889%, 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 1	GERP -0.6, phastCons 0.99
Overall
CADD	7.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.889% East Asian · 398/44,748 alleles

Filtering AF 0.817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.789%

Overall 0.0263% 420/1,596,240 alleles · rare exomes 391/1,444,494 · genomes 29/151,746 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.889%	112
Remaining individualsnot grpmax-eligible	0.00965%	10,364
South Asian	0.0077%	12,979
African / African-American	0.00669%	14,945
European (non-Finnish)	0.000339%	294,821

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.Val875=
Coding: c.2625A>G
MANE Select: NM_006267
dbSNP: rs200515712
Type: single nucleotide variant
Location: chr2:108762123 (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-val875 (accessed [today's date]).

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