Is CAPN2 p.Ala184Thr (c.550G>A) pathogenic?

CAPN2 p.Ala184Thr (c.550G>A) is classified Likely benign in CAPN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-05). AlphaMissense: likely pathogenic (0.9658); Rare (popmax 0.448%, afr).

How common is CAPN2 p.Ala184Thr (c.550G>A) in the general population?

CAPN2 p.Ala184Thr (c.550G>A) is rare (popmax 0.448%, afr) (gnomAD).

What do computational predictors say about CAPN2 p.Ala184Thr (c.550G>A)?

AlphaMissense predicts likely pathogenic (score 0.9658) — an in-silico prediction, not a clinical call.

CAPN2 p.Ala184Thr

c.550G>A · rs147235023 · VCV719166

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9658 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.448%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9658	likely pathogenic
REVEL	0.904	moderately pathogenic-leaning
SaProt	LLR -14.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 62 kb · p 0.00029 · regional, not allelic
Overall
CADD	28.7	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 0.448% African / African-American · 336/75,044 alleles

Filtering AF 0.408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.393%

Overall 0.0287% 464/1,614,184 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.448%	223
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Admixed American	0.0317%	3,159
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.00636%	15,734
East Asian	0.00223%	44,882

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: CAPN2
Protein: p.Ala184Thr
Coding: c.550G>A
MANE Select: NM_001748
dbSNP: rs147235023
Type: single nucleotide variant
Location: chr1:223745429 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 3 PDB
Residue 184: the calpain catalytic domain; an α-helix

Full CAPN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN2 p.Ala248Thr Uncertain significance ★★ ⚠ same type
CAPN2 p.Gly72Asp Uncertain significance ★★ ⚠ same type
CAPN2 p.Asp48= Benign ★★ same type
CAPN2 p.Lys677Gln Benign ★★ ⚠ same type
CAPN2 p.Ala101Pro Uncertain significance ★ ⚠ same type
CAPN2 p.Ala171Asp Uncertain significance ★ ⚠ same type
CAPN2 p.Ala194Ser Uncertain significance ★ ⚠ same type
CAPN2 p.Ala247Pro 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/capn2-p-ala184thr (accessed [today's date]).

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