Is RELN p.Glu505= (c.1515G>A) pathogenic?

RELN p.Glu505= (c.1515G>A) is classified Benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). Ultra-rare (popmax 0.0227%, afr); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Glu505= (c.1515G>A)?

RELN p.Glu505= (c.1515G>A) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Glu505= (c.1515G>A) in the general population?

RELN p.Glu505= (c.1515G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

RELN p.Glu505=

c.1515G>A · rs369617694 · VCV2198509

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -1.7
Overall
CADD	2.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,740 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00124% 20/1,606,612 alleles · ultra-rare exomes 9/1,454,548 · genomes 11/152,064 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,396
Admixed American	0.00335%	29,895
European (non-Finnish)	8.52e-05%	1,173,790

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.Glu505=
Coding: c.1515G>A
MANE Select: NM_005045
dbSNP: rs369617694
Type: single nucleotide variant
Location: chr7:103654132 (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-glu505 (accessed [today's date]).

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