Is RELN p.Asp2369= (c.7107C>T) pathogenic?

RELN p.Asp2369= (c.7107C>T) is classified Likely benign in RELN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). Rare (popmax 0.105%, eas); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Asp2369= (c.7107C>T)?

RELN p.Asp2369= (c.7107C>T) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Asp2369= (c.7107C>T) in the general population?

RELN p.Asp2369= (c.7107C>T) is rare (popmax 0.105%, eas) (gnomAD).

RELN p.Asp2369=

c.7107C>T · rs114339919 · VCV475980

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP 1.8, phastCons 1
Overall
CADD	8.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% East Asian · 47/44,876 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.0102% 164/1,614,198 alleles · rare exomes 133/1,461,884 · genomes 31/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.105%	955
Admixed American	0.0933%	1,072
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Middle Eastern	0.0165%	6,062
South Asian	0.0132%	7,590
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,018
European (non-Finnish)	0.00237%	42,144
African / African-American	0.00133%	75,064

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.Asp2369=
Coding: c.7107C>T
MANE Select: NM_005045
dbSNP: rs114339919
Type: single nucleotide variant
Location: chr7:103539151 (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-asp2369 (accessed [today's date]).

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