Is RNF13 p.His263= (c.789C>T) pathogenic?

RNF13 p.His263= (c.789C>T) is classified Benign in RNF13 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 85.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 73.

What condition is associated with RNF13 p.His263= (c.789C>T)?

RNF13 p.His263= (c.789C>T) is associated with developmental and epileptic encephalopathy, 73 (ClinVar).

RNF13 p.His263=

Q: How common is RNF13 p.His263= (c.789C>T) in the general population?

RNF13 p.His263= (c.789C>T) is common (popmax 85.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is RNF13-related severe early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.789C>T · rs6768054 · VCV1240740

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 85.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

developmental and epileptic encephalopathy, 73

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 -1.2	GERP -1.2, phastCons 0.001
Overall
CADD	3.702	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 85.9% East Asian · 38,472/44,804 alleles

Filtering AF 85.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 84.9%

Overall 69.2% 1,109,937/1,604,344 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	85.9%	1
Admixed American	72.8%	1
Finnishnot grpmax-eligible	71.4%	1
European (non-Finnish)	69.9%	1
South Asian	68.8%	1
Remaining individualsnot grpmax-eligible	68.4%	1
Middle Eastern	66.4%	2
Ashkenazi Jewishnot grpmax-eligible	64.7%	2
Amishnot grpmax-eligible	55.1%	2
African / African-American	46.8%	2

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: RNF13
Protein: p.His263=
Coding: c.789C>T
MANE Select: NM_183381
dbSNP: rs6768054
Type: single nucleotide variant
Location: chr3:149960747 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 2 PDB
Residue 263: a UniProt-annotated variant site (found in a tumor sample; uncertain significance; abolished ability to regulate protein trafficking and localization); a β-strand

Full RNF13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 73 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For RNF13-related severe early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Neonatal

Similar variants

RNF13 p.Arg212Thr Uncertain significance ★★ ⚠ same condition
RNF13 p.Glu301Ter Pathogenic ★ same condition
RNF13 p.Arg217Ser Uncertain significance ★ ⚠ same condition
RNF13 p.Asn88Tyr Uncertain significance ★ ⚠ same condition
RNF13 p.Asp251Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
RNF13 p.Gln300Ter Uncertain significance ★ same condition
RNF13 p.Ile36Val Uncertain significance ★ ⚠ same condition
RNF13 p.Lys205Glu 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/rnf13-p-his263 (accessed [today's date]).

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