Is RELN p.Ile2143= (c.6429C>T) pathogenic?

RELN p.Ile2143= (c.6429C>T) is classified Likely benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-22). Absent from gnomAD v4.1; Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Ile2143= (c.6429C>T)?

RELN p.Ile2143= (c.6429C>T) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Ile2143= (c.6429C>T) in the general population?

RELN p.Ile2143= (c.6429C>T) is absent from gnomAD v4.1 (gnomAD).

RELN p.Ile2143=

c.6429C>T · rs1554374836 · VCV475976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial temporal lobe epilepsy 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 0.28, phastCons 1
Overall
CADD	9.833	PHRED · no single calibrated threshold — expert panels disagree

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: RELN
Protein: p.Ile2143=
Coding: c.6429C>T
MANE Select: NM_005045
dbSNP: rs1554374836
Type: single nucleotide variant
Location: chr7:103545218 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 2143: the egf-like 5 domain

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

Disease context

familial temporal lobe epilepsy 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Norman-Roberts syndrome

Similar variants

RELN c.3912+2T>G Likely pathogenic ★★ same condition
RELN c.7349+2T>C Likely pathogenic ★★ same condition
RELN p.Arg1622Ter Pathogenic/Likely pathogenic ★★ same condition
RELN c.1893-3C>T Uncertain significance ★★ same condition
RELN c.227-3C>T Uncertain significance ★★ same condition
RELN c.2465+5G>T Uncertain significance ★★ same condition
RELN c.6072+3A>G Uncertain significance ★★ same condition
RELN c.6072+4C>G 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/reln-p-ile2143 (accessed [today's date]).

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