Is CA2 c.232+2T>G pathogenic?

CA2 c.232+2T>G is classified Likely pathogenic in CA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-18). Very rare (popmax 8.48e-05%, nfe); Associated with CA2-related disorder.

What condition is associated with CA2 c.232+2T>G?

CA2 c.232+2T>G is associated with CA2-related disorder (ClinVar).

How common is CA2 c.232+2T>G in the general population?

CA2 c.232+2T>G is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CA2 c.232+2T>G

rs1450302081 · VCV2636443

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

CA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ1.00	donor loss · deltas
Pangolin	Δ0.84	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Non-coding constraint	Z 0.44	1 kb window · o/e 0.97 · regional · uncalibrated
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,738 alleles

Overall 0.000657% 1/152,186 alleles · very 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: CA2
Coding: c.232+2T>G
MANE Select: NM_000067
dbSNP: rs1450302081
Type: single nucleotide variant
Location: chr8:85465471 (GRCh38)
Gene constraint: LOEUF 1.491 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.38 · 1249 PDB

Full CA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CA2-related disorder

Similar variants

CA2 p.Lys18Glu Pathogenic ⚠ same condition
CA2 p.Pro236His Pathogenic ⚠ same condition
CA2 p.Tyr51Ter Likely pathogenic same condition
CA2 c.232+1G>A Pathogenic ★★ same type
CA2 p.Gln92Pro Likely pathogenic ★★ same type
CA2 p.Glu204Ter Pathogenic/Likely pathogenic ★★ same type
CA2 p.Tyr193Ter Likely pathogenic ★★ same type
CA2 p.Arg181Cys Uncertain significance ★★ ⚠ 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/ca2-c-232-plus-2t-g (accessed [today's date]).

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