Is RELN p.His3422= (c.10266T>C) pathogenic?

RELN p.His3422= (c.10266T>C) is classified Benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-20). Very rare (popmax 0.00223%, eas); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.His3422= (c.10266T>C)?

RELN p.His3422= (c.10266T>C) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.His3422= (c.10266T>C) in the general population?

RELN p.His3422= (c.10266T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

RELN p.His3422=

c.10266T>C · rs200761409 · VCV2936342

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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.
REVEL	0.141	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.024	GERP -3.9, phastCons 0.031
Overall
CADD	3.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,870 alleles

Overall 6.2e-05% 1/1,614,160 alleles · very rare exomes 0/1,461,860 · genomes 1/152,300 · joint denominator

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.His3422=
Coding: c.10266T>C
MANE Select: NM_005045
dbSNP: rs200761409
Type: single nucleotide variant
Location: chr7:103482887 (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-his3422 (accessed [today's date]).

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