Is CACNG2 p.Asp92Asn (c.274G>A) pathogenic?

CACNG2 p.Asp92Asn (c.274G>A) is classified Uncertain significance in CACNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely pathogenic (0.7072); Very rare (popmax 0.00611%, nfe).

How common is CACNG2 p.Asp92Asn (c.274G>A) in the general population?

CACNG2 p.Asp92Asn (c.274G>A) is very rare (popmax 0.00611%, nfe) (gnomAD).

What do computational predictors say about CACNG2 p.Asp92Asn (c.274G>A)?

AlphaMissense predicts likely pathogenic (score 0.7072) — an in-silico prediction, not a clinical call.

CACNG2 p.Asp92Asn

c.274G>A · VCV3826768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00611%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7072	likely pathogenic
REVEL	0.771	pathogenic-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 138 kb · p 8.6e-08 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00611% European (non-Finnish) · 72/1,179,288 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00477% 77/1,613,240 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00611%	16,379
Remaining individualsnot grpmax-eligible	0.0048%	20,815
African / African-American	0.00133%	74,924
South Asian	0.0011%	91,062

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.Asp92Asn
Coding: c.274G>A
MANE Select: NM_006078
Type: single nucleotide variant
Location: chr22:36587486 (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

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-asp92asn (accessed [today's date]).

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