Is RELN p.Thr82= (c.246C>G) pathogenic?

RELN p.Thr82= (c.246C>G) is classified Benign/Likely benign in RELN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-25). Rare (popmax 0.499%, afr); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Thr82= (c.246C>G)?

RELN p.Thr82= (c.246C>G) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Thr82= (c.246C>G) in the general population?

RELN p.Thr82= (c.246C>G) is rare (popmax 0.499%, afr) (gnomAD).

RELN p.Thr82=

c.246C>G · rs113242008 · VCV212034

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.499%, afr)

Conditions

Norman-Roberts syndrome

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 5.1	GERP 1.6, phastCons 1
Overall
CADD	9.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.499% African / African-American · 374/74,878 alleles

Filtering AF 0.458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.441%

Overall 0.0263% 425/1,613,282 alleles · rare exomes 195/1,461,330 · genomes 230/151,952 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.499%	200
Remaining individualsnot grpmax-eligible	0.0416%	2,403
Admixed American	0.0334%	2,996
Middle Eastern	0.0165%	6,056
European (non-Finnish)	0.000339%	294,898

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.Thr82=
Coding: c.246C>G
MANE Select: NM_005045
dbSNP: rs113242008
Type: single nucleotide variant
Location: chr7:103917166 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 82: the reelin domain

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.Thr82Asn Uncertain significance ★ ⚠ same residue
RELN p.Thr82Ile Likely benign ★ 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-thr82 (accessed [today's date]).

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