Is CAPN1 p.Asp600Glu (c.1800T>A) pathogenic?

CAPN1 p.Asp600Glu (c.1800T>A) is classified Uncertain significance in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely pathogenic (0.8859); Very rare (popmax 0.00348%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAPN1 p.Asp600Glu (c.1800T>A)?

CAPN1 p.Asp600Glu (c.1800T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN1 p.Asp600Glu (c.1800T>A) in the general population?

CAPN1 p.Asp600Glu (c.1800T>A) is very rare (popmax 0.00348%, nfe) (gnomAD).

What do computational predictors say about CAPN1 p.Asp600Glu (c.1800T>A)?

AlphaMissense predicts likely pathogenic (score 0.8859) — an in-silico prediction, not a clinical call.

CAPN1 p.Asp600Glu

c.1800T>A · VCV3263141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00348%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8859	likely pathogenic
REVEL	0.605	indeterminate
SaProt	LLR -10.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.7	GERP -3.4
Regional constraint	o/e 0.85	unconstrained · MANE · 29 kb · p 4.3e-06 · regional, not allelic
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00348% European (non-Finnish) · 41/1,179,848 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00254% 41/1,613,578 alleles · very rare

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.Asp600Glu
Coding: c.1800T>A
MANE Select: NM_005186
Type: single nucleotide variant
Location: chr11:65209854 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB
Residue 600: a binding site; the ef-hand 2 domain; the 'domain iv' 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

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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
CAPN1 p.Arg599His 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-asp600glu (accessed [today's date]).

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