Is RELN p.Ser3347Arg (c.10039A>C) pathogenic?

RELN p.Ser3347Arg (c.10039A>C) is classified Uncertain significance in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-14). AlphaMissense: likely pathogenic (0.5672); Absent from gnomAD v4.1; Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Ser3347Arg (c.10039A>C)?

RELN p.Ser3347Arg (c.10039A>C) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Ser3347Arg (c.10039A>C) in the general population?

RELN p.Ser3347Arg (c.10039A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RELN p.Ser3347Arg (c.10039A>C)?

AlphaMissense predicts likely pathogenic (score 0.5672) — an in-silico prediction, not a clinical call.

RELN p.Ser3347Arg

c.10039A>C · rs1450247215 · VCV1009570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

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
AlphaMissense	0.5672	likely pathogenic
REVEL	0.077	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 17 kb · p 2.7e-07 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RELN
Protein: p.Ser3347Arg
Coding: c.10039A>C
MANE Select: NM_005045
dbSNP: rs1450247215
Type: single nucleotide variant
Location: chr7:103483795 (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-ser3347arg (accessed [today's date]).

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