Is RELN p.Ile1069fs (c.3205del) pathogenic?

RELN p.Ile1069fs (c.3205del) is classified Likely pathogenic in RELN (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with lissencephaly spectrum disorders.

What condition is associated with RELN p.Ile1069fs (c.3205del)?

RELN p.Ile1069fs (c.3205del) is associated with lissencephaly spectrum disorders (ClinVar).

How common is RELN p.Ile1069fs (c.3205del) in the general population?

RELN p.Ile1069fs (c.3205del) is no gnomAD frequency available for this variant (gnomAD).

RELN p.Ile1069fs

c.3205del · rs1831726447 · VCV996629

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

lissencephaly spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 24 of 65
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RELN
Protein: p.Ile1069fs
Coding: c.3205del
MANE Select: NM_005045
dbSNP: rs1831726447
Type: Deletion
Location: chr7:103603432 (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

lissencephaly spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RELN p.Ile1069Val Uncertain significance ★ ⚠ same residue
RELN p.Ile1069= Likely benign ★ same residue
RELN p.Phe2205fs Likely pathogenic same condition
RELN c.8489+4_8489+7del Uncertain significance ★ same condition
RELN p.Leu1734Val Conflicting classifications of pathogenicity ★ ⚠ same condition
RELN p.Gln2109Ter Likely pathogenic same condition
RELN p.Gln417Ter Likely pathogenic same condition
RELN p.Asn492fs Pathogenic ★★ same type

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-ile1069fs (accessed [today's date]).

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