Is CA2 p.Tyr51Ter (c.153T>A) pathogenic?

CA2 p.Tyr51Ter (c.153T>A) is classified Likely pathogenic in CA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-28). Very rare (popmax 0.00167%, amr); Associated with CA2-related disorder.

What condition is associated with CA2 p.Tyr51Ter (c.153T>A)?

CA2 p.Tyr51Ter (c.153T>A) is associated with CA2-related disorder (ClinVar).

How common is CA2 p.Tyr51Ter (c.153T>A) in the general population?

CA2 p.Tyr51Ter (c.153T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

CA2 p.Tyr51Ter

c.153T>A · rs1469283598 · VCV3036420

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

CA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.3	GERP -0.76
Overall
CADD	28.9	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 0.00167% Admixed American · 1/60,030 alleles

Overall 6.84e-05% 1/1,461,884 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
Protein: p.Tyr51Ter
Coding: c.153T>A
MANE Select: NM_000067
dbSNP: rs1469283598
Type: single nucleotide variant
Location: chr8:85465390 (GRCh38)
Gene constraint: LOEUF 1.491 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.38 · 1249 PDB
Residue 51: the alpha-carbonic anhydrase domain

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

Disease context

CA2-related disorder

Similar variants

CA2 p.Tyr51Cys Uncertain significance ★★ ⚠ same residue
CA2 c.232+2T>G Likely pathogenic ★ same condition
CA2 p.Lys18Glu Pathogenic ⚠ same condition
CA2 p.Pro236His 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

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-p-tyr51ter (accessed [today's date]).

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