Is SLC1A2 p.Ile276Ser (c.827T>G) pathogenic?

SLC1A2 p.Ile276Ser (c.827T>G) is classified Likely pathogenic in SLC1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely pathogenic (0.9671); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 41.

What condition is associated with SLC1A2 p.Ile276Ser (c.827T>G)?

SLC1A2 p.Ile276Ser (c.827T>G) is associated with developmental and epileptic encephalopathy, 41 (ClinVar).

How common is SLC1A2 p.Ile276Ser (c.827T>G) in the general population?

SLC1A2 p.Ile276Ser (c.827T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC1A2 p.Ile276Ser (c.827T>G)?

AlphaMissense predicts likely pathogenic (score 0.9671) — an in-silico prediction, not a clinical call.

SLC1A2 p.Ile276Ser

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.827T>G · rs1431104151 · VCV2504082

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 41

Computational evidence

Protein change
AlphaMissense	0.9671	likely pathogenic ✓ concordant with ClinVar
REVEL	0.604	indeterminate
SaProt	LLR -14.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP -0.19, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 47 kb · p 5.4e-15 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: SLC1A2
Protein: p.Ile276Ser
Coding: c.827T>G
MANE Select: NM_004171
dbSNP: rs1431104151
Type: single nucleotide variant
Location: chr11:35301549 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 7 PDB
Residue 276: an α-helix

Full SLC1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 41 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

SLC1A2 p.Pro289Arg Pathogenic/Likely pathogenic ★★ same condition
SLC1A2 p.Ala293Thr Uncertain significance ★★ ⚠ same condition
SLC1A2 p.Ala349Val Uncertain significance ★★ ⚠ same condition
SLC1A2 p.Ala409Thr Uncertain significance ★★ ⚠ same condition
SLC1A2 p.Glu203Lys Uncertain significance ★★ ⚠ same condition
SLC1A2 p.Ile130Thr Uncertain significance ★★ ⚠ same condition
SLC1A2 p.Lys157Glu Uncertain significance ★★ ⚠ same condition
SLC1A2 p.Phe185Leu 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/slc1a2-p-ile276ser (accessed [today's date]).

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