Is RELN p.Phe1971fs (c.5911_5912insAT) pathogenic?

RELN p.Phe1971fs (c.59115912insAT) is classified Pathogenic in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Phe1971fs (c.5911_5912insAT)?

RELN p.Phe1971fs (c.5911_5912insAT) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

RELN p.Phe1971fs

c.5911_5912insAT · VCV4786207

Pathogenic Single submitter

Classification

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 39 of 65
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: RELN
Protein: p.Phe1971fs
Coding: c.5911_5912insAT
MANE Select: NM_005045
Type: Insertion
Location: chr7:103553717 (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.Met1635fs Pathogenic ★ same condition
RELN c.2465+14_2465+15insCCCAAATGTTACAAAC Likely benign ★ same condition
RELN c.4937-9_4937-8insG Likely benign ★ same condition
RELN c.5211-19_5211-18insG Likely benign ★ same condition
RELN c.5211-20_5211-19insG Likely benign ★ same condition
RELN c.578-12_578-11insC Likely benign ★ same condition
RELN c.9369+18_9369+19insG Likely benign ★ same condition
RELN c.3912+2T>G Likely pathogenic ★★ 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-phe1971fs (accessed [today's date]).

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