Is CACNA1E p.Pro1897Ser (c.5689C>T) pathogenic?

CACNA1E p.Pro1897Ser (c.5689C>T) is classified Benign in CACNA1E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely pathogenic (0.8387); Absent from gnomAD v4.1.

How common is CACNA1E p.Pro1897Ser (c.5689C>T) in the general population?

CACNA1E p.Pro1897Ser (c.5689C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CACNA1E p.Pro1897Ser (c.5689C>T)?

AlphaMissense predicts likely pathogenic (score 0.8387) — an in-silico prediction, not a clinical call.

CACNA1E p.Pro1897Ser

c.5689C>T · rs2529257081 · VCV2785588

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8387 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8387	likely pathogenic
REVEL	0.532	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 13 kb · p 0.062 · regional, not allelic
Overall
CADD	23.8	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: CACNA1E
Protein: p.Pro1897Ser
Coding: c.5689C>T
MANE Select: NM_001205293
dbSNP: rs2529257081
Type: single nucleotide variant
Location: chr1:181785722 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.56 · 5 PDB
Residue 1897: a UniProt-annotated variant site (in dee69; uncertain significance)

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

Similar variants

CACNA1E p.Ala702Thr Pathogenic/Likely pathogenic ★★ same type
CACNA1E p.Gly348Arg Pathogenic/Likely pathogenic ★★ same type
CACNA1E p.Gly352Arg Pathogenic/Likely pathogenic ★★ same type
CACNA1E p.Ile603Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
CACNA1E p.Ile701Val Pathogenic ★★ ⚠ same type
CACNA1E p.Leu228Pro Pathogenic/Likely pathogenic ★★ same type
CACNA1E p.Phe698Leu Pathogenic/Likely pathogenic ★★ same type
CACNA1E c.3719+1G>A 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-pro1897ser (accessed [today's date]).

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