Is RELN p.Val1214= (c.3642C>T) pathogenic?

RELN p.Val1214= (c.3642C>T) is classified Conflicting classifications of pathogenicity in RELN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-13). Very rare (popmax 0.00879%, sas); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Val1214= (c.3642C>T)?

RELN p.Val1214= (c.3642C>T) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Val1214= (c.3642C>T) in the general population?

RELN p.Val1214= (c.3642C>T) is very rare (popmax 0.00879%, sas) (gnomAD).

RELN p.Val1214=

c.3642C>T · rs151252449 · VCV358406

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00879%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -3.6
Overall
CADD	1.819	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00879% South Asian · 8/91,064 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00465% 75/1,613,818 alleles · very rare exomes 65/1,461,722 · genomes 10/152,096 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00937%	10,669
South Asiangrpmax	0.00879%	11,383
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	0.00449%	22,262
African / African-American	0.00267%	37,450
East Asian	0.00223%	44,882

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1214=
Coding: c.3642C>T
MANE Select: NM_005045
dbSNP: rs151252449
Type: single nucleotide variant
Location: chr7:103594390 (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.Val1214Ala 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-val1214 (accessed [today's date]).

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