Is CAPS2 p.Lys288Gln (c.862A>C) pathogenic?

CAPS2 p.Lys288Gln (c.862A>C) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: ambiguous (0.4164); Rare (popmax 0.166%, sas).

How common is CAPS2 p.Lys288Gln (c.862A>C) in the general population?

CAPS2 p.Lys288Gln (c.862A>C) is rare (popmax 0.166%, sas) (gnomAD).

What do computational predictors say about CAPS2 p.Lys288Gln (c.862A>C)?

AlphaMissense predicts ambiguous (score 0.4164) — an in-silico prediction, not a clinical call.

CAPS2 p.Lys288Gln

c.862A>C · VCV3263270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4164 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.166%, sas)

Computational evidence

Protein change
AlphaMissense	0.4164	ambiguous
REVEL	0.167	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K345Q vs ClinVar K288Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.166% South Asian · 151/91,072 alleles

Filtering AF 0.144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.012% 193/1,614,042 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.166%	603
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.00246%	40,686
Finnishnot grpmax-eligible	0.00156%	64,032

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: CAPS2
Protein: p.Lys288Gln
Coding: c.862A>C
MANE Select: NM_017954 · reported on NM_001355024
Type: single nucleotide variant
Location: chr12:75298755 (GRCh38)
Structure: AlphaFold pLDDT 79.91

Full CAPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CADPS2 c.3718-15A>C Benign ★★ same type
CADPS2 p.Ala298Thr Benign ★★ same type
CADPS2 p.Asp1088Asn Likely benign ★★ ⚠ same type
CADPS2 p.Glu1010Lys Benign ★★ same type
CADPS2 p.Leu154= Likely benign ★★ same type
CADPS2 p.Lys338= Benign ★★ same type
CADPS2 p.Met828Val Benign ★★ same type
CADPS2 p.Thr819= Benign ★★ 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/caps2-p-lys288gln (accessed [today's date]).

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