Is CACNA1A p.Phe627= (c.1881C>T) pathogenic?

CACNA1A p.Phe627= (c.1881C>T) is classified Likely benign in CACNA1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-27). Very rare (popmax 0.0072%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CACNA1A p.Phe627= (c.1881C>T)?

CACNA1A p.Phe627= (c.1881C>T) is associated with Inborn genetic diseases, episodic ataxia type 2, developmental and epileptic encephalopathy, 42 (ClinVar).

How common is CACNA1A p.Phe627= (c.1881C>T) in the general population?

CACNA1A p.Phe627= (c.1881C>T) is very rare (popmax 0.0072%, nfe) (gnomAD).

CACNA1A p.Phe627=

c.1881C>T · rs371268760 · VCV1132442

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.98	GERP -5.5
Overall
CADD	6.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0072% European (non-Finnish) · 85/1,179,904 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00595% 96/1,613,886 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,411
European (non-Finnish)grpmax	0.0072%	13,881
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
African / African-American	0.00267%	37,464
East Asian	0.00223%	44,898
South Asian	0.0011%	91,080

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CACNA1A
Protein: p.Phe627=
Coding: c.1881C>T
MANE Select: NM_001127222
dbSNP: rs371268760
Type: single nucleotide variant
Location: chr19:13308152 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.34 · 4 PDB
Residue 627: an α-helix

Full CACNA1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: episodic ataxia type 2 developmental and epileptic encephalopathy, 42

Similar variants

CACNA1A p.Phe627Leu Uncertain significance ★ ⚠ same residue
CACNA1A c.1082+1G>A Pathogenic ★★ same condition
CACNA1A c.1198+1G>A Pathogenic/Likely pathogenic ★★ same condition
CACNA1A c.2105-2A>G Likely pathogenic ★★ same condition
CACNA1A c.3692+1G>A Pathogenic/Likely pathogenic ★★ same condition
CACNA1A c.3822+1G>A Pathogenic ★★ same condition
CACNA1A c.3989+1G>A Pathogenic ★★ same condition
CACNA1A c.3989+1G>T 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/cacna1a-p-phe627 (accessed [today's date]).

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