Is RELN p.Asp3271= (c.9813T>C) pathogenic?

RELN p.Asp3271= (c.9813T>C) is classified Likely benign in RELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-18). Very rare (popmax 0.00333%, amr); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Asp3271= (c.9813T>C)?

RELN p.Asp3271= (c.9813T>C) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Asp3271= (c.9813T>C) in the general population?

RELN p.Asp3271= (c.9813T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

RELN p.Asp3271=

c.9813T>C · rs780599729 · VCV793097

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Norman-Roberts syndrome

⚠ 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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.5	GERP 0.91, phastCons 1
Overall
CADD	10.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,614,080 alleles · very rare exomes 2/1,461,870 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
South Asian	0.0011%	91,086
European (non-Finnish)	0.000169%	590,016

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.Asp3271=
Coding: c.9813T>C
MANE Select: NM_005045
dbSNP: rs780599729
Type: single nucleotide variant
Location: chr7:103486367 (GRCh38)

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

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-asp3271 (accessed [today's date]).

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