Is RELN p.Lys2437Arg (c.7310A>G) pathogenic?

RELN p.Lys2437Arg (c.7310A>G) is classified Likely benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.106); Ultra-rare (popmax 0.015%, amr); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Lys2437Arg (c.7310A>G)?

RELN p.Lys2437Arg (c.7310A>G) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Lys2437Arg (c.7310A>G) in the general population?

RELN p.Lys2437Arg (c.7310A>G) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about RELN p.Lys2437Arg (c.7310A>G)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

RELN p.Lys2437Arg

c.7310A>G · rs762951578 · VCV475986

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

familial temporal lobe epilepsy 7

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.192	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 67 kb · p 2.1e-16 · regional, not allelic
Overall
CADD	22.9	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

Grpmax group 0.015% Admixed American · 9/59,994 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000558% 9/1,614,050 alleles · ultra-rare exomes 9/1,461,768 · genomes 0/152,282 · 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: RELN
Protein: p.Lys2437Arg
Coding: c.7310A>G
MANE Select: NM_005045
dbSNP: rs762951578
Type: single nucleotide variant
Location: chr7:103535355 (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 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-lys2437arg (accessed [today's date]).

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