Is RELN p.Val2832Ala (c.8495T>C) pathogenic?

RELN p.Val2832Ala (c.8495T>C) is classified Uncertain significance in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-20). AlphaMissense: likely benign (0.2947); Very rare (popmax 8.48e-05%, nfe); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Val2832Ala (c.8495T>C)?

RELN p.Val2832Ala (c.8495T>C) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Val2832Ala (c.8495T>C) in the general population?

RELN p.Val2832Ala (c.8495T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about RELN p.Val2832Ala (c.8495T>C)?

AlphaMissense predicts likely benign (score 0.2947) — an in-silico prediction, not a clinical call.

RELN p.Val2832Ala

c.8495T>C · rs1257978206 · VCV1039279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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	0.2947	likely benign
REVEL	0.235	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 67 kb · p 2.1e-16 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,926 alleles

Overall 6.2e-05% 1/1,614,080 alleles · very rare exomes 1/1,461,760 · genomes 0/152,320 · 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.Val2832Ala
Coding: c.8495T>C
MANE Select: NM_005045
dbSNP: rs1257978206
Type: single nucleotide variant
Location: chr7:103500917 (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-val2832ala (accessed [today's date]).

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