Is CAPN10 p.Pro200= (c.600A>G) pathogenic?

CAPN10 p.Pro200= (c.600A>G) is classified Benign in CAPN10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 19.2%, sas) — too common for a highly-penetrant pathogenic allele; Associated with CAPN10-related disorder.

What condition is associated with CAPN10 p.Pro200= (c.600A>G)?

CAPN10 p.Pro200= (c.600A>G) is associated with CAPN10-related disorder (ClinVar).

CAPN10 p.Pro200=

Q: How common is CAPN10 p.Pro200= (c.600A>G) in the general population?

CAPN10 p.Pro200= (c.600A>G) is common (popmax 19.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.600A>G · rs3792269 · VCV3056633

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 19.2%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

CAPN10-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.3	GERP -2.1
Overall
CADD	0.279	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.2% South Asian · 17,363/90,212 alleles

Filtering AF 19% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.9%

Overall 15.8% 254,633/1,608,754 alleles · common exomes 235,490/1,456,466 · genomes 19,143/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	19.2%	5
Finnishnot grpmax-eligible	19.1%	5
European (non-Finnish)	16.9%	6
Amishnot grpmax-eligible	15.2%	7
Remaining individualsnot grpmax-eligible	15%	7
Middle Eastern	13.8%	7
East Asian	9.18%	11
Ashkenazi Jewishnot grpmax-eligible	8.9%	11
Admixed American	8.78%	11
African / African-American	4.46%	22

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: CAPN10
Protein: p.Pro200=
Coding: c.600A>G
MANE Select: NM_023083
dbSNP: rs3792269
Type: single nucleotide variant
Location: chr2:240592062 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 200: the calpain catalytic domain; a UniProt-annotated variant site (in)

Full CAPN10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAPN10-related disorder

Similar variants

CAPN10 p.Pro200Thr Benign ★★ same residue
CAPN10 c.1989+1G>A Pathogenic ★ same condition
CAPN10 p.Ala380= Uncertain significance ★ same condition
CAPN10 p.Arg395Gln Uncertain significance ★ ⚠ same condition
CAPN10 p.Lys366Thr Uncertain significance ⚠ same condition
CAPN10 c.1990-7T>C Benign same condition
CAPN10 p.Ala390= Likely benign same condition
CAPN10 p.Ala447= Likely benign 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/capn10-p-pro200 (accessed [today's date]).

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