Is CA11 p.Pro325Arg (c.974C>G) pathogenic?

CA11 p.Pro325Arg (c.974C>G) is classified Uncertain significance in CA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.0788); Absent from gnomAD v4.1.

How common is CA11 p.Pro325Arg (c.974C>G) in the general population?

CA11 p.Pro325Arg (c.974C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA11 p.Pro325Arg (c.974C>G)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

CA11 p.Pro325Arg

c.974C>G · VCV4217499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,343,598)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.04	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 7.4	GERP -0.39, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 7,510 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	22.9	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

No allele count reported in gnomAD v4.1 (AN 1,343,598). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CA11
Protein: p.Pro325Arg
Coding: c.974C>G
MANE Select: NM_001217
Type: single nucleotide variant
Location: chr19:48638132 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 88.39
Residue 325: the 'disordered' region

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

Similar variants

CA11 p.Pro325Leu Uncertain significance ★ ⚠ same residue
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

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-pro325arg (accessed [today's date]).

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