Is CAPS2 p.Arg279Gly (c.835A>G) pathogenic?

CAPS2 p.Arg279Gly (c.835A>G) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.6634); Very rare (popmax 0.00596%, nfe).

How common is CAPS2 p.Arg279Gly (c.835A>G) in the general population?

CAPS2 p.Arg279Gly (c.835A>G) is very rare (popmax 0.00596%, nfe) (gnomAD).

What do computational predictors say about CAPS2 p.Arg279Gly (c.835A>G)?

AlphaMissense predicts likely pathogenic (score 0.6634) — an in-silico prediction, not a clinical call.

CAPS2 p.Arg279Gly

c.835A>G · VCV3995324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00596%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6634	likely pathogenic
REVEL	0.415	indeterminate
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.39	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.43	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.5, phastCons 1
Overall
CADD	28.4	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 R336G vs ClinVar R279G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00596% European (non-Finnish) · 70/1,174,686 alleles

Filtering AF 0.0048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00441%

Overall 0.00454% 73/1,606,308 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00596%	16,781
Admixed American	0.00168%	59,366
Remaining individualsnot grpmax-eligible	0.00161%	62,182
Finnishnot grpmax-eligible	0.00156%	63,988

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.Arg279Gly
Coding: c.835A>G
MANE Select: NM_017954 · reported on NM_001355024
Type: single nucleotide variant
Location: chr12:75298872 (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-arg279gly (accessed [today's date]).

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