Is RELN p.Gln532= (c.1596G>A) pathogenic?

RELN p.Gln532= (c.1596G>A) is classified Benign in RELN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 7.23%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Gln532= (c.1596G>A)?

RELN p.Gln532= (c.1596G>A) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

RELN p.Gln532=

Q: How common is RELN p.Gln532= (c.1596G>A) in the general population?

RELN p.Gln532= (c.1596G>A) is common (popmax 7.23%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1596G>A · rs41276154 · VCV95212

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 7.23%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Norman-Roberts syndrome

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 2.3	GERP -1.3, phastCons 1
Overall
CADD	7.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.23% African / African-American · 5,413/74,916 alleles

Filtering AF 7.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 7%

Overall 2.91% 46,899/1,612,708 alleles · common exomes 41,046/1,460,632 · genomes 5,853/152,076 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.23%	14
European (non-Finnish)	3.04%	33
Remaining individualsnot grpmax-eligible	2.65%	38
Finnishnot grpmax-eligible	2.21%	45
Ashkenazi Jewishnot grpmax-eligible	1.88%	53
Admixed American	1.86%	54
Middle Eastern	1.09%	92
South Asian	0.852%	117
Amishnot grpmax-eligible	0.219%	456
East Asian	0.0134%	7,470

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.Gln532=
Coding: c.1596G>A
MANE Select: NM_005045
dbSNP: rs41276154
Type: single nucleotide variant
Location: chr7:103652718 (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

Norman-Roberts syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial temporal lobe epilepsy 7

Similar variants

RELN p.Gln532Ter Pathogenic ★ 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-gln532 (accessed [today's date]).

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