Is CAPS p.Leu18= (c.54G>A) pathogenic?

CAPS p.Leu18= (c.54G>A) is classified Likely benign in CAPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Rare (popmax 0.317%, mid); Associated with CAPS-related disorder.

What condition is associated with CAPS p.Leu18= (c.54G>A)?

CAPS p.Leu18= (c.54G>A) is associated with CAPS-related disorder (ClinVar).

How common is CAPS p.Leu18= (c.54G>A) in the general population?

CAPS p.Leu18= (c.54G>A) is rare (popmax 0.317%, mid) (gnomAD).

CAPS p.Leu18=

c.54G>A · rs61743888 · VCV3043112

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.317%, mid)

Conditions

CAPS-related disorder

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 0.79	GERP -1.7
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.317% Middle Eastern · 19/5,990 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.0184% 282/1,536,180 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.317%	315
Admixed American	0.049%	2,040
Remaining individualsnot grpmax-eligible	0.025%	4,002
Finnishnot grpmax-eligible	0.0225%	4,453
European (non-Finnish)	0.0176%	5,678
South Asian	0.00714%	14,011
African / African-American	0.00547%	18,293
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,654

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: CAPS
Protein: p.Leu18=
Coding: c.54G>A
MANE Select: NM_003716 · reported on NM_004058
dbSNP: rs61743888
Type: single nucleotide variant
Location: chr19:5914127 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 18: the 'disordered' region

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

Disease context

CAPS-related disorder

Similar variants

CAPS p.Arg18His Benign ★★ ⚠ same residue
CAPS p.Arg18= Likely benign ★ same residue
CADPS c.3477+2T>G Uncertain significance ★ same condition
CADPS p.Ala564Val Uncertain significance ★ ⚠ same condition
CADPS p.Arg1198Ile Uncertain significance ★ ⚠ same condition
CADPS p.Gln1260= Uncertain significance ★ same condition
CADPS p.Gly1335Arg Uncertain significance ⚠ same condition
CADPS p.Leu1289Val 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/caps-p-leu18 (accessed [today's date]).

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