Is CACNG2 p.Leu76= (c.228G>T) pathogenic?

CACNG2 p.Leu76= (c.228G>T) is classified Benign in CACNG2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-21). Rare (popmax 0.485%, sas); Associated with CACNG2-related disorder.

What condition is associated with CACNG2 p.Leu76= (c.228G>T)?

CACNG2 p.Leu76= (c.228G>T) is associated with CACNG2-related disorder (ClinVar).

How common is CACNG2 p.Leu76= (c.228G>T) in the general population?

CACNG2 p.Leu76= (c.228G>T) is rare (popmax 0.485%, sas) (gnomAD).

CACNG2 p.Leu76=

c.228G>T · rs571563795 · VCV3036720

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.485%, sas)

Conditions

CACNG2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.6, phastCons 1
Overall
CADD	8.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.485% South Asian · 442/91,076 alleles

Filtering AF 0.448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.433%

Overall 0.0285% 460/1,613,252 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.485%	206
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Admixed American	0.00167%	60,020
European (non-Finnish)	8.48e-05%	1,179,124

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: CACNG2
Protein: p.Leu76=
Coding: c.228G>T
MANE Select: NM_006078
dbSNP: rs571563795
Type: single nucleotide variant
Location: chr22:36587532 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 5 PDB

Full CACNG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CACNG2-related disorder

Similar variants

CACNG2 p.Ala100Ser Uncertain significance ★★ ⚠ same type
CACNG2 p.Ala214Thr Uncertain significance ★★ ⚠ same type
CACNG2 p.Arg319Pro Uncertain significance ★★ ⚠ same type
CACNG2 p.Gln298Arg Uncertain significance ★★ ⚠ same type
CACNG2 p.Glu126Lys Uncertain significance ★★ ⚠ same type
CACNG2 c.212-12C>A Likely benign ★★ same type
CACNG2 p.Val193= Likely benign ★★ same type
CACNG2 c.436+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/cacng2-p-leu76 (accessed [today's date]).

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