Is CA8 p.Arg78Ter (c.232C>T) pathogenic?

CA8 p.Arg78Ter (c.232C>T) is classified Pathogenic in CA8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-05). Very rare (popmax 0.000169%, nfe); Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3.

What condition is associated with CA8 p.Arg78Ter (c.232C>T)?

CA8 p.Arg78Ter (c.232C>T) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (ClinVar).

How common is CA8 p.Arg78Ter (c.232C>T) in the general population?

CA8 p.Arg78Ter (c.232C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Dysequilibrium syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CA8 p.Arg78Ter

c.232C>T · VCV3335815

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3

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 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.34, phastCons 1
Overall
CADD	38.0	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 0.000169% European (non-Finnish) · 2/1,180,004 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,900 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: CA8
Protein: p.Arg78Ter
Coding: c.232C>T
MANE Select: NM_004056
Type: single nucleotide variant
Location: chr8:60279749 (GRCh38)
Gene constraint: LOEUF 0.698 · pLI 0.24 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 1 PDB
Residue 78: the alpha-carbonic anhydrase domain; a β-strand

Full CA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysequilibrium syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CA8 c.100+85T>C Benign ★★ same condition
CA8 c.-103T>C Benign ★★ same condition
CA8 c.-54A>C Benign ★★ same condition
CA8 p.Glu109= Benign ★★ same condition
CA8 p.Arg275Trp Likely pathogenic ★ same condition
CA8 p.Asn84Thr Likely pathogenic ★ same condition
CA8 p.Lys159Ter Likely pathogenic ★ same condition
CA8 p.Trp233Cys Uncertain significance ★ ⚠ same condition

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/ca8-p-arg78ter (accessed [today's date]).

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