Is CAPN5 p.Arg570Cys (c.1708C>T) pathogenic?

CAPN5 p.Arg570Cys (c.1708C>T) is classified Likely benign in CAPN5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.2326); Ultra-rare (popmax 0.0747%, sas).

How common is CAPN5 p.Arg570Cys (c.1708C>T) in the general population?

CAPN5 p.Arg570Cys (c.1708C>T) is ultra-rare (popmax 0.0747%, sas) (gnomAD).

What do computational predictors say about CAPN5 p.Arg570Cys (c.1708C>T)?

AlphaMissense predicts likely benign (score 0.2326) — an in-silico prediction, not a clinical call.

CAPN5 p.Arg570Cys

c.1708C>T · rs782363480 · VCV1114648

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2326 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0747%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2326	likely benign
REVEL	0.674	pathogenic-leaning
SaProt	LLR -12.48	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.76, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	31.0	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 0.0747% South Asian · 68/91,064 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0552%

Overall 0.00582% 94/1,613,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0747%	1,339
Middle Eastern	0.0169%	5,902
Remaining individualsnot grpmax-eligible	0.00961%	10,411
East Asian	0.00668%	14,960
European (non-Finnish)	0.00136%	73,746

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.Arg570Cys
Coding: c.1708C>T
MANE Select: NM_004055
dbSNP: rs782363480
Type: single nucleotide variant
Location: chr11:77122680 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 570: the c2 domain

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

Similar variants

CAPN5 p.Arg570His Uncertain significance ★★ ⚠ same residue
CAPN5 p.Arg570Ser 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-arg570cys (accessed [today's date]).

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