Is CAPN5 p.Asp320= (c.960C>T) pathogenic?

CAPN5 p.Asp320= (c.960C>T) is classified Likely benign in CAPN5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Ultra-rare (popmax 0.0396%, sas).

How common is CAPN5 p.Asp320= (c.960C>T) in the general population?

CAPN5 p.Asp320= (c.960C>T) is ultra-rare (popmax 0.0396%, sas) (gnomAD).

CAPN5 p.Asp320=

c.960C>T · rs782454728 · VCV1124693

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0396%, sas)

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 -12	GERP -3.2
Overall
CADD	5.918	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0396% South Asian · 36/90,810 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0259%

Overall 0.00285% 46/1,613,112 alleles · ultra-rare exomes 42/1,460,952 · genomes 4/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0396%	2,523
Middle Eastern	0.0165%	6,078
Admixed American	0.00501%	19,976
Remaining individualsnot grpmax-eligible	0.0016%	62,456
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000339%	294,897

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: CAPN5
Protein: p.Asp320=
Coding: c.960C>T
MANE Select: NM_004055
dbSNP: rs782454728
Type: single nucleotide variant
Location: chr11:77116292 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 320: the calpain catalytic domain

Full CAPN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN5 p.Asp320Asn Uncertain significance ★ ⚠ same residue
CAPN5 p.Asp320Gly Uncertain significance ★ ⚠ same residue
CAPN5 p.Arg243Leu Pathogenic ★★ same type
CAPN5 p.Arg289Trp Pathogenic ★★ ⚠ same type
CAPN5 p.Ala118Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala185Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala237Val 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/capn5-p-asp320 (accessed [today's date]).

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