Is SYNE1 p.Ile6426Val (c.19276A>G) pathogenic?

SYNE1 p.Ile6426Val (c.19276A>G) is classified Uncertain significance in SYNE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1327); Absent from gnomAD v4.1; Associated with autosomal recessive ataxia, Beauce type.

What condition is associated with SYNE1 p.Ile6426Val (c.19276A>G)?

SYNE1 p.Ile6426Val (c.19276A>G) is associated with autosomal recessive ataxia, Beauce type, Emery-Dreifuss muscular dystrophy 4, autosomal dominant (ClinVar).

How common is SYNE1 p.Ile6426Val (c.19276A>G) in the general population?

SYNE1 p.Ile6426Val (c.19276A>G) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive ataxia, Beauce type inherited?

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

What do computational predictors say about SYNE1 p.Ile6426Val (c.19276A>G)?

AlphaMissense predicts likely benign (score 0.1327) — an in-silico prediction, not a clinical call.

SYNE1 p.Ile6426Val

c.19276A>G · VCV4791219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1327 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

autosomal recessive ataxia, Beauce type

Computational evidence

Protein change
AlphaMissense	0.1327	likely benign
REVEL	0.036	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 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 126 kb · p 0.027 · regional, not allelic
Overall
CADD	19.4	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

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: SYNE1
Protein: p.Ile6426Val
Coding: c.19276A>G
MANE Select: NM_182961
Type: single nucleotide variant
Location: chr6:152255074 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)

Full SYNE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive ataxia, Beauce type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Emery-Dreifuss muscular dystrophy 4, autosomal dominant

For Autosomal recessive ataxia, Beauce type (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Childhood, Neonatal

Similar variants

SYNE1 p.Ile6426Leu Uncertain significance ★★ ⚠ same residue
SYNE1 c.10145+1G>A Pathogenic/Likely pathogenic ★★ same condition
SYNE1 c.12079-2A>T Likely pathogenic ★★ same condition
SYNE1 c.15918-12A>G Pathogenic ★★ same condition
SYNE1 c.16390-2A>G Pathogenic/Likely pathogenic ★★ same condition
SYNE1 c.17682+1G>A Likely pathogenic ★★ same condition
SYNE1 c.19260+2T>C Likely pathogenic ★★ same condition
SYNE1 c.22044+1G>A Likely pathogenic ★★ 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/syne1-p-ile6426val (accessed [today's date]).

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