Is RELN p.Pro969= (c.2907A>G) pathogenic?

RELN p.Pro969= (c.2907A>G) is classified Benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Ultra-rare (popmax 0.0859%, sas); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Pro969= (c.2907A>G)?

RELN p.Pro969= (c.2907A>G) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Pro969= (c.2907A>G) in the general population?

RELN p.Pro969= (c.2907A>G) is ultra-rare (popmax 0.0859%, sas) (gnomAD).

RELN p.Pro969=

c.2907A>G · rs780891394 · VCV707455

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0859%, sas)

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 -0.34	GERP -3.7, phastCons 0.016
Overall
CADD	6.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0859% South Asian · 78/90,780 alleles

Filtering AF 0.0705% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0648%

Overall 0.00531% 85/1,600,000 alleles · ultra-rare exomes 83/1,447,824 · genomes 2/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0859%	1,164
Remaining individualsnot grpmax-eligible	0.00806%	12,407
Admixed American	0.00334%	29,984

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.Pro969=
Coding: c.2907A>G
MANE Select: NM_005045
dbSNP: rs780891394
Type: single nucleotide variant
Location: chr7:103610796 (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 p.Pro969Ala Uncertain significance ★ 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-pro969 (accessed [today's date]).

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