Is CA13 p.Ala143Pro (c.427G>C) pathogenic?

CA13 p.Ala143Pro (c.427G>C) is classified Uncertain significance in CA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9832); Absent from gnomAD v4.1.

How common is CA13 p.Ala143Pro (c.427G>C) in the general population?

CA13 p.Ala143Pro (c.427G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA13 p.Ala143Pro (c.427G>C)?

AlphaMissense predicts likely pathogenic (score 0.9832) — an in-silico prediction, not a clinical call.

CA13 p.Ala143Pro

c.427G>C · VCV4647373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9832 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9832	likely pathogenic · top 1% in CA13
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -16.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 36 kb · p 0.83 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CA13
Protein: p.Ala143Pro
Coding: c.427G>C
MANE Select: NM_198584
Type: single nucleotide variant
Location: chr8:85266680 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.74 · 18 PDB
Residue 143: the alpha-carbonic anhydrase domain; a β-strand

Full CA13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA13 p.Ala234Gly Uncertain significance ★ ⚠ same type
CA13 p.Ala240Thr Uncertain significance ★ ⚠ same type
CA13 p.Arg247His Uncertain significance ★ ⚠ same type
CA13 p.Arg255Cys Uncertain significance ★ ⚠ same type
CA13 p.Arg81His Uncertain significance ★ ⚠ same type
CA13 p.Arg9Cys Uncertain significance ★ ⚠ same type
CA13 p.Asn245Asp Uncertain significance ★ ⚠ same type
CA13 p.Gln28His 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/ca13-p-ala143pro (accessed [today's date]).

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