Is CACNA1E p.Ser855fs (c.2562del) pathogenic?

CACNA1E p.Ser855fs (c.2562del) is classified Uncertain significance in CACNA1E (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Absent from gnomAD v4.1.

How common is CACNA1E p.Ser855fs (c.2562del) in the general population?

CACNA1E p.Ser855fs (c.2562del) is absent from gnomAD v4.1 (gnomAD).

CACNA1E p.Ser855fs

c.2562del · VCV3363249

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,502,692)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 20 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -16	GERP -4.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,502,692). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CACNA1E
Protein: p.Ser855fs
Coding: c.2562del
MANE Select: NM_001205293
Type: Deletion
Location: chr1:181732643 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.56 · 5 PDB
Residue 855: a UniProt-annotated variant site (in dee69; uncertain significance); the 'disordered' region; a modified residue (phosphoserine)

Full CACNA1E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNA1E p.Ser855Phe Uncertain significance ★ ⚠ same residue
CACNA1E c.3731+10_3731+13del Likely benign ★★ same type
CACNA1E c.5140-12del Benign ★★ same type
CACNA1E p.Thr301fs Likely pathogenic ★ same type
CACNA1E c.1171+11_1171+28del Uncertain significance ★ same type
CACNA1E c.372+5_372+18del Uncertain significance ★ same type
CACNA1E c.5578+4del Uncertain significance ★ same type
CACNA1E p.806NPL[1] 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/cacna1e-p-ser855fs (accessed [today's date]).

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