Is RELN p.Ala3276Ser (c.9826G>T) pathogenic?

RELN p.Ala3276Ser (c.9826G>T) is classified Uncertain significance in RELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-28). AlphaMissense: likely benign (0.0675); Very rare (popmax 0.00333%, amr); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Ala3276Ser (c.9826G>T)?

RELN p.Ala3276Ser (c.9826G>T) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Ala3276Ser (c.9826G>T) in the general population?

RELN p.Ala3276Ser (c.9826G>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about RELN p.Ala3276Ser (c.9826G>T)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

RELN p.Ala3276Ser

c.9826G>T · rs781713047 · VCV2081718

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

familial temporal lobe epilepsy 7

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 2.1, phastCons 0.93
Regional constraint	o/e 0.69	unconstrained · MANE · 17 kb · p 2.7e-07 · regional, not allelic
Overall
CADD	19.54	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 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,614,100 alleles · very rare exomes 3/1,461,870 · genomes 0/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
South Asian	0.0011%	91,074

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.Ala3276Ser
Coding: c.9826G>T
MANE Select: NM_005045
dbSNP: rs781713047
Type: single nucleotide variant
Location: chr7:103486354 (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

familial temporal lobe epilepsy 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Norman-Roberts syndrome

Similar variants

RELN c.3912+2T>G Likely pathogenic ★★ same condition
RELN c.7349+2T>C Likely pathogenic ★★ same condition
RELN p.Arg1622Ter Pathogenic/Likely pathogenic ★★ same condition
RELN c.1893-3C>T Uncertain significance ★★ same condition
RELN c.227-3C>T Uncertain significance ★★ same condition
RELN c.2465+5G>T Uncertain significance ★★ same condition
RELN c.6072+3A>G Uncertain significance ★★ same condition
RELN c.6072+4C>G 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-ala3276ser (accessed [today's date]).

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