Is CAPN1 p.Asp356= (c.1068C>T) pathogenic?

CAPN1 p.Asp356= (c.1068C>T) is classified Likely benign in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). Ultra-rare (popmax 0.0267%, afr); Associated with Inborn genetic diseases.

What condition is associated with CAPN1 p.Asp356= (c.1068C>T)?

CAPN1 p.Asp356= (c.1068C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN1 p.Asp356= (c.1068C>T) in the general population?

CAPN1 p.Asp356= (c.1068C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

CAPN1 p.Asp356=

c.1068C>T · VCV3827180

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Conditions

Inborn genetic diseases

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 -11	GERP -5.3
Overall
CADD	4.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/75,044 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00204% 33/1,613,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,752
Middle Eastern	0.0165%	6,062
East Asian	0.00669%	14,957
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Admixed American	0.00167%	60,018
European (non-Finnish)	0.000509%	196,642

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: CAPN1
Protein: p.Asp356=
Coding: c.1068C>T
MANE Select: NM_005186
Type: single nucleotide variant
Location: chr11:65188649 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB
Residue 356: the 'domain iii' region

Full CAPN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAPN1 p.Asp356Tyr Uncertain significance ★★ ⚠ same residue
CAPN1 p.Arg104His Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg293Gln Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg293Trp Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg347Cys Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg347His Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg48Gln Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg581Gln Uncertain significance ★★ ⚠ 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/capn1-p-asp356 (accessed [today's date]).

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