Is CAPN5 p.Ala48= (c.144C>T) pathogenic?

CAPN5 p.Ala48= (c.144C>T) is classified Likely benign in CAPN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-08). Very rare (popmax 0.00223%, eas).

How common is CAPN5 p.Ala48= (c.144C>T) in the general population?

CAPN5 p.Ala48= (c.144C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CAPN5 p.Ala48=

c.144C>T · VCV4913088

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -20	GERP -2.9
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00105% 17/1,613,446 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
African / African-American	0.00133%	74,956
European (non-Finnish)	0.00127%	78,669

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.Ala48=
Coding: c.144C>T
MANE Select: NM_004055
Type: single nucleotide variant
Location: chr11:77085030 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 48: the calpain catalytic domain

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

Similar variants

CAPN5 p.Ala48Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CAPN5 p.Ala48Val 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-ala48 (accessed [today's date]).

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