Is RELN p.Ser2964fs (c.8891_8892del) pathogenic?

RELN p.Ser2964fs (c.88918892del) is classified Likely pathogenic in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Ser2964fs (c.8891_8892del)?

RELN p.Ser2964fs (c.8891_8892del) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

RELN p.Ser2964fs

c.8891_8892del · VCV3594192

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Norman-Roberts syndrome

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 55 of 65
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: RELN
Protein: p.Ser2964fs
Coding: c.8891_8892del
MANE Select: NM_005045
Type: Microsatellite
Location: chr7:103497878 (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 p.Glu2134del Uncertain significance ★★ same condition
RELN p.Ile310del Uncertain significance ★★ same condition
RELN p.Phe38del Uncertain significance ★★ same condition
RELN p.Cys225_Glu226delinsTer Pathogenic ★ same condition
RELN p.Tyr1484fs Pathogenic ★ same condition
RELN c.2895+3_2895+6del Uncertain significance ★ same condition
RELN c.8668-9_8668-5del Conflicting classifications of pathogenicity ★ same condition
RELN p.Asn2436del 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-ser2964fs (accessed [today's date]).

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