Is CA2 p.Lys113= (c.339A>G) pathogenic?

CA2 p.Lys113= (c.339A>G) is classified Conflicting classifications of pathogenicity in CA2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-08). Very rare (popmax 0.00365%, nfe); Associated with autosomal recessive osteopetrosis 3.

What condition is associated with CA2 p.Lys113= (c.339A>G)?

CA2 p.Lys113= (c.339A>G) is associated with autosomal recessive osteopetrosis 3 (ClinVar).

How common is CA2 p.Lys113= (c.339A>G) in the general population?

CA2 p.Lys113= (c.339A>G) is very rare (popmax 0.00365%, 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 p.Lys113=

c.339A>G · rs370128128 · VCV1482044

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00365%, 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 0.36	GERP -2.8, phastCons 0.025
Overall
CADD	7.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00365% European (non-Finnish) · 41/1,123,774 alleles

Filtering AF 0.00271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00277% 43/1,552,358 alleles · very rare exomes 41/1,400,144 · genomes 2/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00365%	27,409
Remaining individualsnot grpmax-eligible	0.00331%	30,225

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.Lys113=
Coding: c.339A>G
MANE Select: NM_000067
dbSNP: rs370128128
Type: single nucleotide variant
Location: chr8:85473799 (GRCh38)
Gene constraint: LOEUF 1.491 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.38 · 1249 PDB
Residue 113: the alpha-carbonic anhydrase domain

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-p-lys113 (accessed [today's date]).

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