Is RELN p.Asp1020= (c.3060C>T) pathogenic?

RELN p.Asp1020= (c.3060C>T) is classified Benign/Likely benign in RELN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Rare (popmax 0.602%, eas); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Asp1020= (c.3060C>T)?

RELN p.Asp1020= (c.3060C>T) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Asp1020= (c.3060C>T) in the general population?

RELN p.Asp1020= (c.3060C>T) is rare (popmax 0.602%, eas) (gnomAD).

RELN p.Asp1020=

c.3060C>T · rs115886170 · VCV358409

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.602%, eas)

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 -6.2	GERP -3.8
Overall
CADD	0.722	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.602% East Asian · 270/44,848 alleles

Filtering AF 0.543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.52%

Overall 0.0195% 314/1,613,876 alleles · rare exomes 261/1,461,596 · genomes 53/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.602%	166
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.00878%	11,385
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)	0.00127%	78,657

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.Asp1020=
Coding: c.3060C>T
MANE Select: NM_005045
dbSNP: rs115886170
Type: single nucleotide variant
Location: chr7:103604432 (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 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
RELN c.6072+4C>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-asp1020 (accessed [today's date]).

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