Is CAPS2 p.Arg247Cys (c.739C>T) pathogenic?

CAPS2 p.Arg247Cys (c.739C>T) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.2611); Ultra-rare (popmax 0.0193%, sas).

How common is CAPS2 p.Arg247Cys (c.739C>T) in the general population?

CAPS2 p.Arg247Cys (c.739C>T) is ultra-rare (popmax 0.0193%, sas) (gnomAD).

What do computational predictors say about CAPS2 p.Arg247Cys (c.739C>T)?

AlphaMissense predicts likely benign (score 0.2611) — an in-silico prediction, not a clinical call.

CAPS2 p.Arg247Cys

c.739C>T · VCV3484919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2611 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2611	likely benign
REVEL	0.715	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.33	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 0.41, phastCons 1
Overall
CADD	26.3	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 R304C vs ClinVar R247C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% South Asian · 15/77,806 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00954%

Overall 0.00443% 65/1,468,340 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0193%	5,187
African / African-American	0.0185%	5,416
Remaining individualsnot grpmax-eligible	0.0035%	28,536
European (non-Finnish)	0.00307%	32,523
East Asian	0.00239%	41,920
Admixed American	0.00196%	50,974

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.Arg247Cys
Coding: c.739C>T
MANE Select: NM_017954 · reported on NM_001355024
Type: single nucleotide variant
Location: chr12:75299838 (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-arg247cys (accessed [today's date]).

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