Is CAPN5 p.Pro47Ser (c.139C>T) pathogenic?

CAPN5 p.Pro47Ser (c.139C>T) is classified Uncertain significance in CAPN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely benign (0.0847); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Pro47Ser (c.139C>T)?

CAPN5 p.Pro47Ser (c.139C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN5 p.Pro47Ser (c.139C>T) in the general population?

CAPN5 p.Pro47Ser (c.139C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CAPN5 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

CAPN5 p.Pro47Ser

c.139C>T · VCV3827272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	16.56	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00118% 19/1,613,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.011%	9,109
Remaining individualsnot grpmax-eligible	0.0048%	20,833
African / African-American	0.00133%	75,078
European (non-Finnish)	0.000339%	295,008

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.Pro47Ser
Coding: c.139C>T
MANE Select: NM_004055
Type: single nucleotide variant
Location: chr11:77085025 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 47: the calpain catalytic domain

Full CAPN5 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

CAPN5 p.Pro47= Likely benign ★ same residue
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala34Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala357Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala362Gly Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala447Thr 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/capn5-p-pro47ser (accessed [today's date]).

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