Is CA8 p.Gly162Arg (c.484G>A) pathogenic?

CA8 p.Gly162Arg (c.484G>A) is classified Pathogenic in CA8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.9882); Very rare (popmax 0.00017%, nfe); Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3.

What condition is associated with CA8 p.Gly162Arg (c.484G>A)?

CA8 p.Gly162Arg (c.484G>A) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (ClinVar).

How common is CA8 p.Gly162Arg (c.484G>A) in the general population?

CA8 p.Gly162Arg (c.484G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Dysequilibrium syndrome inherited?

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

What do computational predictors say about CA8 p.Gly162Arg (c.484G>A)?

AlphaMissense predicts likely pathogenic (score 0.9882) — an in-silico prediction, not a clinical call.

CA8 p.Gly162Arg

c.484G>A · VCV3335814

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3

Computational evidence

Protein change
AlphaMissense	0.9882	likely pathogenic ✓ concordant with ClinVar
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -15.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 57 kb · p 0.00026 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,770 alleles

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

Overall 0.000137% 2/1,461,576 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.Gly162Arg
Coding: c.484G>A
MANE Select: NM_004056
Type: single nucleotide variant
Location: chr8:60232313 (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 162: the alpha-carbonic anhydrase domain

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-gly162arg (accessed [today's date]).

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