Is CAPN12 p.Gly22Arg (c.64G>A) pathogenic?

CAPN12 p.Gly22Arg (c.64G>A) is classified Likely benign in CAPN12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: likely benign (0.0791); Rare (popmax 0.148%, mid).

How common is CAPN12 p.Gly22Arg (c.64G>A) in the general population?

CAPN12 p.Gly22Arg (c.64G>A) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about CAPN12 p.Gly22Arg (c.64G>A)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

CAPN12 p.Gly22Arg

c.64G>A · rs565347573 · VCV2395393

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -4.5
Regional constraint	o/e 1.14	unconstrained · MANE · 13 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	0.016	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 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00353% 57/1,614,148 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
East Asian	0.0178%	5,610
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	0.00254%	39,334
Admixed American	0.00167%	60,016
Finnishnot grpmax-eligible	0.00156%	64,008
South Asian	0.0011%	91,084

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: CAPN12
Protein: p.Gly22Arg
Coding: c.64G>A
MANE Select: NM_144691
dbSNP: rs565347573
Type: single nucleotide variant
Location: chr19:38744102 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63

Full CAPN12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN12 p.Gly22Glu Uncertain significance ★ ⚠ same residue
CAPN12 c.1362+80A>G Benign ★★ same type
CAPN12 c.1374+85A>C Benign ★★ same type
CAPN12 c.1583+12G>A Benign ★★ same type
CAPN12 c.1584-39C>T Benign ★★ same type
CAPN12 c.1686+152A>G Benign ★★ same type
CAPN12 c.1745-17C>T Benign ★★ same type
CAPN12 c.1815+25G>A Benign ★★ 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/capn12-p-gly22arg (accessed [today's date]).

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