Is RANBP2 p.Ser1514= (c.4542T>C) pathogenic?

RANBP2 p.Ser1514= (c.4542T>C) is classified Likely benign in RANBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-12). Very rare (popmax 0.00223%, eas); Associated with familial acute necrotizing encephalopathy.

What condition is associated with RANBP2 p.Ser1514= (c.4542T>C)?

RANBP2 p.Ser1514= (c.4542T>C) is associated with familial acute necrotizing encephalopathy (ClinVar).

How common is RANBP2 p.Ser1514= (c.4542T>C) in the general population?

RANBP2 p.Ser1514= (c.4542T>C) is very rare (popmax 0.00223%, 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.Ser1514=

c.4542T>C · rs2149276093 · VCV1107916

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, 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 -0.014	GERP -0.12
Overall
CADD	3.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,868 alleles

Overall 6.2e-05% 1/1,614,020 alleles · very rare exomes 1/1,461,760 · genomes 0/152,260 · joint denominator

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.Ser1514=
Coding: c.4542T>C
MANE Select: NM_006267
dbSNP: rs2149276093
Type: single nucleotide variant
Location: chr2:108765081 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)
Residue 1514: the '22 x 2 aa repeats of f-g' 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

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-ser1514 (accessed [today's date]).

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