Is CA11 p.Trp252Cys (c.756G>C) pathogenic?

CA11 p.Trp252Cys (c.756G>C) is classified Uncertain significance in CA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). AlphaMissense: likely pathogenic (0.9949); Absent from gnomAD v4.1.

How common is CA11 p.Trp252Cys (c.756G>C) in the general population?

CA11 p.Trp252Cys (c.756G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA11 p.Trp252Cys (c.756G>C)?

AlphaMissense predicts likely pathogenic (score 0.9949) — an in-silico prediction, not a clinical call.

CA11 p.Trp252Cys

c.756G>C · VCV3262570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9949 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9949	likely pathogenic · top 3% in CA11
REVEL	0.843	moderately pathogenic-leaning
SaProt	LLR -14.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 7,510 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	33.0	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: CA11
Protein: p.Trp252Cys
Coding: c.756G>C
MANE Select: NM_001217
Type: single nucleotide variant
Location: chr19:48639344 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 88.39
Residue 252: the alpha-carbonic anhydrase domain

Full CA11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA11 p.Ala139Asp Uncertain significance ★ ⚠ same type
CA11 p.Ala143Pro Uncertain significance ★ ⚠ same type
CA11 p.Ala191Thr Uncertain significance ★ ⚠ same type
CA11 p.Ala63Thr Uncertain significance ★ ⚠ same type
CA11 p.Arg209His Uncertain significance ★ ⚠ same type
CA11 p.Arg289Trp Uncertain significance ★ ⚠ same type
CA11 p.Arg318His Uncertain significance ★ ⚠ same type
CA11 p.Arg318Leu 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/ca11-p-trp252cys (accessed [today's date]).

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