Is RNF13 p.Arg217Ser (c.651A>T) pathogenic?

RNF13 p.Arg217Ser (c.651A>T) is classified Uncertain significance in RNF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-10). AlphaMissense: likely pathogenic (0.9966); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 73.

What condition is associated with RNF13 p.Arg217Ser (c.651A>T)?

RNF13 p.Arg217Ser (c.651A>T) is associated with developmental and epileptic encephalopathy, 73 (ClinVar).

How common is RNF13 p.Arg217Ser (c.651A>T) in the general population?

RNF13 p.Arg217Ser (c.651A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF13 p.Arg217Ser (c.651A>T)?

AlphaMissense predicts likely pathogenic (score 0.9966) — an in-silico prediction, not a clinical call.

RNF13 p.Arg217Ser

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.651A>T · VCV3377055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 73

Computational evidence

Protein change
AlphaMissense	0.9966	likely pathogenic
REVEL	0.335	indeterminate
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -0.55, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 115 kb · p 0.00025 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RNF13
Protein: p.Arg217Ser
Coding: c.651A>T
MANE Select: NM_183381
Type: single nucleotide variant
Location: chr3:149921178 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 2 PDB

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.His263= Benign ★★ same condition
RNF13 p.Glu301Ter Pathogenic ★ 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-arg217ser (accessed [today's date]).

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