Is VAMP8 p.Ile26Val (c.76A>G) pathogenic?

VAMP8 p.Ile26Val (c.76A>G) is classified Uncertain significance in VAMP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.2501); Absent from gnomAD v4.1.

How common is VAMP8 p.Ile26Val (c.76A>G) in the general population?

VAMP8 p.Ile26Val (c.76A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VAMP8 p.Ile26Val (c.76A>G)?

AlphaMissense predicts likely benign (score 0.2501) — an in-silico prediction, not a clinical call.

VAMP8 p.Ile26Val

c.76A>G · VCV4603450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2501 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2501	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -7.34	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,066 bp · p 0.08 · regional, not allelic
Overall
CADD	22.3	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: VAMP8
Protein: p.Ile26Val
Coding: c.76A>G
MANE Select: NM_003761
Type: single nucleotide variant
Location: chr2:85579081 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.56 · 2 PDB
Residue 26: an α-helix; the v-snare coiled-coil homology domain

Full VAMP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VAMP8 c.*143T>C Benign ★★ same type
VAMP8 p.Arg12Cys Uncertain significance ★ ⚠ same type
VAMP8 p.Arg12Pro Uncertain significance ★ ⚠ same type
VAMP8 p.Arg37Trp Uncertain significance ★ ⚠ same type
VAMP8 p.Arg45Cys Uncertain significance ★ ⚠ same type
VAMP8 p.Asn10Ser Uncertain significance ★ ⚠ same type
VAMP8 p.Asn40Asp Uncertain significance ★ ⚠ same type
VAMP8 p.Asn40Ile 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/vamp8-p-ile26val (accessed [today's date]).

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