Is RELN p.Asp3250= (c.9750C>T) pathogenic?

RELN p.Asp3250= (c.9750C>T) is classified Conflicting classifications of pathogenicity in RELN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.0275%, sas); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Asp3250= (c.9750C>T)?

RELN p.Asp3250= (c.9750C>T) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Asp3250= (c.9750C>T) in the general population?

RELN p.Asp3250= (c.9750C>T) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

RELN p.Asp3250=

c.9750C>T · rs539337691 · VCV290106

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Conditions

familial temporal lobe epilepsy 7

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.42	GERP -4.2
Overall
CADD	6.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% South Asian · 25/91,036 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00415% 67/1,614,042 alleles · ultra-rare exomes 61/1,461,740 · genomes 6/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,641
Finnishnot grpmax-eligible	0.0125%	8,004
European (non-Finnish)	0.00271%	36,875
East Asian	0.00223%	44,842
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Asp3250=
Coding: c.9750C>T
MANE Select: NM_005045
dbSNP: rs539337691
Type: single nucleotide variant
Location: chr7:103489755 (GRCh38)

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

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-asp3250 (accessed [today's date]).

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