Is CAPS2 p.Asp116Glu (c.348T>A) pathogenic?

CAPS2 p.Asp116Glu (c.348T>A) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.1138); Ultra-rare (popmax 0.0125%, afr).

How common is CAPS2 p.Asp116Glu (c.348T>A) in the general population?

CAPS2 p.Asp116Glu (c.348T>A) is ultra-rare (popmax 0.0125%, afr) (gnomAD).

What do computational predictors say about CAPS2 p.Asp116Glu (c.348T>A)?

AlphaMissense predicts likely benign (score 0.1138) — an in-silico prediction, not a clinical call.

CAPS2 p.Asp116Glu

c.348T>A · VCV3827341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1138 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1138	likely benign
REVEL	0.122	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 -0.79	GERP -3.2
Overall
CADD	3.245	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D173E vs ClinVar D116E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% African / African-American · 9/71,872 alleles

Filtering AF 0.00647% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00485%

Overall 0.000587% 9/1,533,096 alleles · ultra-rare

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.Asp116Glu
Coding: c.348T>A
MANE Select: NM_017954 · reported on NM_001355024
Type: single nucleotide variant
Location: chr12:75321406 (GRCh38)
Structure: AlphaFold pLDDT 79.91

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

Similar variants

CAPS2 p.Asp116Gly 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-asp116glu (accessed [today's date]).

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