Is RELN p.Val2370= (c.7110T>C) pathogenic?

RELN p.Val2370= (c.7110T>C) is classified Benign in RELN (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). Common (popmax 20.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Val2370= (c.7110T>C)?

RELN p.Val2370= (c.7110T>C) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

RELN p.Val2370=

Q: How common is RELN p.Val2370= (c.7110T>C) in the general population?

RELN p.Val2370= (c.7110T>C) is common (popmax 20.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7110T>C · rs362746 · VCV95228

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 20.2%, eas) — 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 -0.62	GERP -3.6
Overall
CADD	1.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.2% East Asian · 9,068/44,878 alleles

Filtering AF 19.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.7%

Overall 2.88% 46,453/1,614,178 alleles · common exomes 42,889/1,461,876 · genomes 3,564/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	20.2%	5
South Asian	7.15%	14
Remaining individualsnot grpmax-eligible	3.22%	31
European (non-Finnish)	2.26%	44
Finnishnot grpmax-eligible	1.86%	54
Ashkenazi Jewishnot grpmax-eligible	1.07%	93
Middle Eastern	0.841%	119
Admixed American	0.576%	173
Amishnot grpmax-eligible	0.439%	228
African / African-American	0.424%	236

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.Val2370=
Coding: c.7110T>C
MANE Select: NM_005045
dbSNP: rs362746
Type: single nucleotide variant
Location: chr7:103539148 (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.Val2370Ala Uncertain significance ★ same residue
RELN p.Val2370Ile Conflicting classifications of pathogenicity ★ ⚠ 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

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-val2370 (accessed [today's date]).

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