Is CAPN10 p.Pro549= (c.1647C>T) pathogenic?

CAPN10 p.Pro549= (c.1647C>T) is classified Likely benign in CAPN10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-29). Rare (popmax 0.334%, eas); Associated with CAPN10-related disorder.

What condition is associated with CAPN10 p.Pro549= (c.1647C>T)?

CAPN10 p.Pro549= (c.1647C>T) is associated with CAPN10-related disorder (ClinVar).

How common is CAPN10 p.Pro549= (c.1647C>T) in the general population?

CAPN10 p.Pro549= (c.1647C>T) is rare (popmax 0.334%, eas) (gnomAD).

CAPN10 p.Pro549=

c.1647C>T · rs17846979 · VCV3033484

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.334%, eas)

Conditions

CAPN10-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP -16	GERP -2.9
Overall
CADD	0.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.334% East Asian · 150/44,886 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.274%

Overall 0.0132% 213/1,613,576 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.334%	299
South Asian	0.0417%	2,397
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Middle Eastern	0.0165%	6,060
African / African-American	0.00266%	37,540
Admixed American	0.00167%	60,022
Finnishnot grpmax-eligible	0.00158%	63,428
European (non-Finnish)	0.000508%	196,668

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: CAPN10
Protein: p.Pro549=
Coding: c.1647C>T
MANE Select: NM_023083
dbSNP: rs17846979
Type: single nucleotide variant
Location: chr2:240596846 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 549: the 'domain iii 2' region

Full CAPN10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAPN10-related disorder

Similar variants

CAPN10 c.1989+1G>A Pathogenic ★ same condition
CAPN10 p.Ala380= Uncertain significance ★ same condition
CAPN10 p.Arg395Gln Uncertain significance ★ ⚠ same condition
CAPN10 p.Lys366Thr Uncertain significance ⚠ same condition
CAPN10 c.1990-7T>C Benign same condition
CAPN10 p.Ala390= Likely benign same condition
CAPN10 p.Ala447= Likely benign same condition
CAPN10 p.Ala450= Likely benign 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/capn10-p-pro549 (accessed [today's date]).

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