Is CAPS2 p.Cys119Arg (c.355T>C) pathogenic?

CAPS2 p.Cys119Arg (c.355T>C) is classified Benign in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-22). AlphaMissense: likely benign (0.1027); Low-frequency (popmax 1.27%, eas).

How common is CAPS2 p.Cys119Arg (c.355T>C) in the general population?

CAPS2 p.Cys119Arg (c.355T>C) is low-frequency (popmax 1.27%, eas) (gnomAD).

What do computational predictors say about CAPS2 p.Cys119Arg (c.355T>C)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

CAPS2 p.Cys119Arg

c.355T>C · rs142559838 · VCV782877

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.152	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -3.4
Overall
CADD	0.447	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 C176R vs ClinVar C119R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.27% East Asian · 516/40,700 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.14%

Overall 0.0422% 649/1,537,410 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.27%	79
Remaining individualsnot grpmax-eligible	0.185%	541
African / African-American	0.0179%	5,576
South Asian	0.00498%	20,092
Admixed American	0.00417%	23,988
European (non-Finnish)	0.00035%	285,416

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.Cys119Arg
Coding: c.355T>C
MANE Select: NM_017954 · reported on NM_001355024
dbSNP: rs142559838
Type: single nucleotide variant
Location: chr12:75316434 (GRCh38)
Structure: AlphaFold pLDDT 79.91

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

Similar variants

CAPS2 p.Cys119Tyr Uncertain significance ★ ⚠ same residue
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

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-cys119arg (accessed [today's date]).

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