Is CA11 p.Arg6Cys (c.16C>T) pathogenic?

CA11 p.Arg6Cys (c.16C>T) is classified Uncertain significance in CA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.3964); Ultra-rare (popmax 0.0242%, amr).

How common is CA11 p.Arg6Cys (c.16C>T) in the general population?

CA11 p.Arg6Cys (c.16C>T) is ultra-rare (popmax 0.0242%, amr) (gnomAD).

What do computational predictors say about CA11 p.Arg6Cys (c.16C>T)?

AlphaMissense predicts ambiguous (score 0.3964) — an in-silico prediction, not a clinical call.

CA11 p.Arg6Cys

c.16C>T · VCV3483731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3964 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3964	ambiguous
REVEL	0.23	benign-leaning
SaProt	LLR -8.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP -3.5, phastCons 0.001
Regional constraint	o/e 0.79	unconstrained · MANE · 7,510 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	18.91	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0242% Admixed American · 14/57,904 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0042% 67/1,596,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0242%	4,136
Middle Eastern	0.0167%	5,982
Remaining individualsnot grpmax-eligible	0.0113%	8,825
East Asian	0.00456%	21,928
European (non-Finnish)	0.00358%	27,906
African / African-American	0.00134%	74,454

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: CA11
Protein: p.Arg6Cys
Coding: c.16C>T
MANE Select: NM_001217
Type: single nucleotide variant
Location: chr19:48645617 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 88.39

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

Similar variants

CA11 p.Arg6Pro 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-arg6cys (accessed [today's date]).

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