Is RELN p.Ile2901= (c.8703C>A) pathogenic?

RELN p.Ile2901= (c.8703C>A) is classified Conflicting classifications of pathogenicity in RELN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-27). Very rare (popmax 0.00667%, amr); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Ile2901= (c.8703C>A)?

RELN p.Ile2901= (c.8703C>A) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Ile2901= (c.8703C>A) in the general population?

RELN p.Ile2901= (c.8703C>A) is very rare (popmax 0.00667%, amr) (gnomAD).

RELN p.Ile2901=

c.8703C>A · rs367803009 · VCV197971

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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 5.2	GERP 1.8, phastCons 1
Overall
CADD	8.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,970 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00198% 32/1,613,802 alleles · very rare exomes 28/1,461,776 · genomes 4/152,026 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,993
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.00203%	49,164
African / African-American	0.00134%	74,870

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.Ile2901=
Coding: c.8703C>A
MANE Select: NM_005045
dbSNP: rs367803009
Type: single nucleotide variant
Location: chr7:103498217 (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-ile2901 (accessed [today's date]).

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