Is RELN p.Ser1042= (c.3126A>C) pathogenic?

RELN p.Ser1042= (c.3126A>C) is classified Likely benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). Very rare (popmax 0.00267%, afr); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Ser1042= (c.3126A>C)?

RELN p.Ser1042= (c.3126A>C) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Ser1042= (c.3126A>C) in the general population?

RELN p.Ser1042= (c.3126A>C) is very rare (popmax 0.00267%, afr) (gnomAD).

RELN p.Ser1042=

c.3126A>C · rs773562211 · VCV2049251

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -12	GERP -3.8
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,920 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,742 alleles · very rare exomes 0/1,461,520 · genomes 2/152,222 · 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.Ser1042=
Coding: c.3126A>C
MANE Select: NM_005045
dbSNP: rs773562211
Type: single nucleotide variant
Location: chr7:103604366 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 1042: the egf-like 2 domain

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.Ser1042Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RELN p.Ser1042Thr 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

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-ser1042 (accessed [today's date]).

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