Is SPTBN1 p.Gly826Val (c.2477G>T) pathogenic?

SPTBN1 p.Gly826Val (c.2477G>T) is classified Uncertain significance in SPTBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-17). AlphaMissense: likely benign (0.2564); Absent from gnomAD v4.1.

How common is SPTBN1 p.Gly826Val (c.2477G>T) in the general population?

SPTBN1 p.Gly826Val (c.2477G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPTBN1 p.Gly826Val (c.2477G>T)?

AlphaMissense predicts likely benign (score 0.2564) — an in-silico prediction, not a clinical call.

SPTBN1 p.Gly826Val

c.2477G>T · VCV3573877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2564 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2564	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -3.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 3,895 bp · p 5.2e-09 · regional, not allelic
Overall
CADD	23.6	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 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: SPTBN1
Protein: p.Gly826Val
Coding: c.2477G>T
MANE Select: NM_003128
Type: single nucleotide variant
Location: chr2:54629611 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.52 · 3 PDB
Residue 826: a UniProt-annotated variant site (in ddisba; affects function in neuronal axonal growth; decreased interaction with sptan1; disturbs cytoskeleton organization and dynamics)

Full SPTBN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPTBN1 p.Ala1086Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
SPTBN1 p.Arg1054Ter Likely pathogenic ★★ same type
SPTBN1 p.Arg1745Ter Pathogenic ★★ same type
SPTBN1 p.Val271Met Likely pathogenic ★★ same type
SPTBN1 c.6356+7C>T Uncertain significance ★★ same type
SPTBN1 p.Ala297Gly Uncertain significance ★★ ⚠ same type
SPTBN1 p.Arg2140Leu Uncertain significance ★★ ⚠ same type
SPTBN1 p.Arg2325Cys Uncertain significance ★★ same type

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/sptbn1-p-gly826val (accessed [today's date]).

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