Is RELN p.His3003Gln (c.9009C>G) pathogenic?

RELN p.His3003Gln (c.9009C>G) is classified Likely benign in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.1345); Very rare (popmax 0.000593%, nfe); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.His3003Gln (c.9009C>G)?

RELN p.His3003Gln (c.9009C>G) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.His3003Gln (c.9009C>G) in the general population?

RELN p.His3003Gln (c.9009C>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about RELN p.His3003Gln (c.9009C>G)?

AlphaMissense predicts likely benign (score 0.1345) — an in-silico prediction, not a clinical call.

RELN p.His3003Gln

c.9009C>G · rs750882329 · VCV861924

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1345 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/2 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	0.1345	likely benign
REVEL	0.236	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.6	GERP -3.6
Regional constraint	o/e 0.80	unconstrained · MANE · 67 kb · p 2.1e-16 · regional, not allelic
Overall
CADD	1.215	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

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,972 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,062 alleles · very rare exomes 7/1,461,794 · genomes 0/152,268 · joint denominator

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.His3003Gln
Coding: c.9009C>G
MANE Select: NM_005045
dbSNP: rs750882329
Type: single nucleotide variant
Location: chr7:103496710 (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-his3003gln (accessed [today's date]).

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