Is RANBP2 p.Val548= (c.1644A>G) pathogenic?

RANBP2 p.Val548= (c.1644A>G) is classified Benign/Likely benign in RANBP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0423%, eas); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Val548= (c.1644A>G)?

RANBP2 p.Val548= (c.1644A>G) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Val548= (c.1644A>G) in the general population?

RANBP2 p.Val548= (c.1644A>G) is ultra-rare (popmax 0.0423%, 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.Val548=

c.1644A>G · rs1057955 · VCV1600141

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, 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 0.71	GERP 0.57, phastCons 0.97
Overall
CADD	5.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0423% East Asian · 19/44,886 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00372% 60/1,611,830 alleles · ultra-rare exomes 49/1,459,608 · genomes 11/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,362
South Asian	0.033%	3,032
Remaining individualsnot grpmax-eligible	0.00321%	31,146
African / African-American	0.00267%	37,430
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000509%	196,642

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.Val548=
Coding: c.1644A>G
MANE Select: NM_006267
dbSNP: rs1057955
Type: single nucleotide variant
Location: chr2:108751883 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)
Residue 548: a UniProt-annotated variant site (in)

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.Val548Leu Likely benign ★★ same residue
RANBP2 p.Val548Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
RANBP2 p.Val548Ile Uncertain significance ★ ⚠ same residue
RANBP2 p.Val548Ser 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

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-val548 (accessed [today's date]).

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