Is CA5B p.Arg63Cys (c.187C>T) pathogenic?

CA5B p.Arg63Cys (c.187C>T) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1756); Ultra-rare (popmax 0.044%, amr).

How common is CA5B p.Arg63Cys (c.187C>T) in the general population?

CA5B p.Arg63Cys (c.187C>T) is ultra-rare (popmax 0.044%, amr) (gnomAD).

What do computational predictors say about CA5B p.Arg63Cys (c.187C>T)?

AlphaMissense predicts likely benign (score 0.1756) — an in-silico prediction, not a clinical call.

CA5B p.Arg63Cys

c.187C>T · rs779251569 · VCV3136137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1756	likely benign
REVEL	0.688	pathogenic-leaning
SaProt	LLR -10.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.046, phastCons 0.98
Regional constraint	o/e 0.28	constrained · MANE · 152 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	23.3	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 0.044% Admixed American · 17/38,650 alleles

Filtering AF 0.028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00162% 19/1,171,987 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.044%	2,274
South Asian	0.00203%	49,305
European (non-Finnish)	0.000114%	880,747

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: CA5B
Protein: p.Arg63Cys
Coding: c.187C>T
MANE Select: NM_007220
dbSNP: rs779251569
Type: single nucleotide variant
Location: chrX:15764622 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 63: the alpha-carbonic anhydrase domain

Full CA5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA5B p.Ala135Pro Uncertain significance ★ ⚠ same type
CA5B p.Ala138Val Uncertain significance ★ ⚠ same type
CA5B p.Ala170Glu Uncertain significance ★ ⚠ same type
CA5B p.Ala47Val Uncertain significance ★ ⚠ same type
CA5B p.Arg282Cys Uncertain significance ★ ⚠ same type
CA5B p.Arg282His Uncertain significance ★ ⚠ same type
CA5B p.Arg290Leu Uncertain significance ★ ⚠ same type
CA5B p.Arg293His 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/ca5b-p-arg63cys (accessed [today's date]).

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