Is CA2 p.Lys39Gln (c.115A>C) pathogenic?

CA2 p.Lys39Gln (c.115A>C) is classified Uncertain significance in CA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0887); Absent from gnomAD v4.1.

How common is CA2 p.Lys39Gln (c.115A>C) in the general population?

CA2 p.Lys39Gln (c.115A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA2 p.Lys39Gln (c.115A>C)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

CA2 p.Lys39Gln

c.115A>C · rs2536478754 · VCV2001896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.7
Regional constraint	o/e 0.92	unconstrained · MANE · 9,714 bp · p 0.33 · regional, not allelic
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CA2
Protein: p.Lys39Gln
Coding: c.115A>C
MANE Select: NM_000067
dbSNP: rs2536478754
Type: single nucleotide variant
Location: chr8:85465352 (GRCh38)
Gene constraint: LOEUF 1.491 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.38 · 1249 PDB
Residue 39: the alpha-carbonic anhydrase domain; a β-strand

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

Similar variants

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
CA2 p.Arg181Cys Uncertain significance ★★ ⚠ same type
CA2 p.Arg181His Uncertain significance ★★ ⚠ same type
CA2 p.Arg226His Uncertain significance ★★ ⚠ same type
CA2 p.Arg245Cys Uncertain significance ★★ ⚠ 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-lys39gln (accessed [today's date]).

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