Is CA2 c.*17G>A pathogenic?

CA2 c.17G>A is classified Uncertain significance in CA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.146%, nfe); Associated with autosomal recessive osteopetrosis 3.

What condition is associated with CA2 c.*17G>A?

CA2 c.*17G>A is associated with autosomal recessive osteopetrosis 3 (ClinVar).

How common is CA2 c.*17G>A in the general population?

CA2 c.*17G>A is rare (popmax 0.146%, nfe) (gnomAD).

How is Osteopetrosis with renal tubular acidosis inherited?

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

CA2 c.*17G>A

rs140653628 · VCV363837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.146%, nfe)

Conditions

autosomal recessive osteopetrosis 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.026	GERP -1.1
Non-coding constraint	Z -0.07	1 kb window · o/e 1.01 · regional · uncalibrated
Overall
CADD	2.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.146% European (non-Finnish) · 1,723/1,179,334 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.138%

Overall 0.113% 1,829/1,613,088 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.146%	684
Remaining individualsnot grpmax-eligible	0.0609%	1,642
South Asian	0.0296%	3,373
Admixed American	0.0284%	3,527
African / African-American	0.028%	3,572
Middle Eastern	0.0165%	6,054
Finnishnot grpmax-eligible	0.00313%	31,974

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.*17G>A
MANE Select: NM_000067
dbSNP: rs140653628
Type: single nucleotide variant
Location: chr8:85480806 (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

autosomal recessive osteopetrosis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Osteopetrosis with renal tubular acidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CA2 c.232+1G>A Pathogenic ★★ same condition
CA2 p.Gln92Pro Likely pathogenic ★★ same condition
CA2 p.Glu204Ter Pathogenic/Likely pathogenic ★★ same condition
CA2 p.Tyr193Ter Likely pathogenic ★★ same condition
CA2 p.Arg181Cys Uncertain significance ★★ ⚠ same condition
CA2 p.Arg181His Uncertain significance ★★ ⚠ same condition
CA2 p.Arg226His Uncertain significance ★★ ⚠ same condition
CA2 p.Asn67Asp 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/ca2-c-star-17g-a (accessed [today's date]).

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