Is RELN p.Leu720Val (c.2158C>G) pathogenic?

RELN p.Leu720Val (c.2158C>G) is classified Uncertain significance in RELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-11-18). AlphaMissense: likely benign (0.1518); Absent from gnomAD v4.1; Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Leu720Val (c.2158C>G)?

RELN p.Leu720Val (c.2158C>G) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Leu720Val (c.2158C>G) in the general population?

RELN p.Leu720Val (c.2158C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RELN p.Leu720Val (c.2158C>G)?

AlphaMissense predicts likely benign (score 0.1518) — an in-silico prediction, not a clinical call.

RELN p.Leu720Val

c.2158C>G · rs1554395337 · VCV542562

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1518 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial temporal lobe epilepsy 7

Computational evidence

Protein change
AlphaMissense	0.1518	likely benign
REVEL	0.294	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 432 kb · p 0.0016 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Leu720Val
Coding: c.2158C>G
MANE Select: NM_005045
dbSNP: rs1554395337
Type: single nucleotide variant
Location: chr7:103636380 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

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 p.Leu720= Likely benign ★ same residue
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

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-leu720val (accessed [today's date]).

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