Is CA5B p.Arg297Gln (c.890G>A) pathogenic?

CA5B p.Arg297Gln (c.890G>A) is classified Likely benign in CA5B (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-26). AlphaMissense: likely benign (0.0749); Very rare (popmax 0.00593%, eas).

How common is CA5B p.Arg297Gln (c.890G>A) in the general population?

CA5B p.Arg297Gln (c.890G>A) is very rare (popmax 0.00593%, eas) (gnomAD).

What do computational predictors say about CA5B p.Arg297Gln (c.890G>A)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

CA5B p.Arg297Gln

c.890G>A · rs759792043 · VCV2303680

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -7.05	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 0.56	GERP -0.28, phastCons 0.061
Regional constraint	o/e 1.05	unconstrained · MANE · 18 kb · p 0.53 · regional, not allelic
Overall
CADD	1.115	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 0.00593% East Asian · 2/33,740 alleles

Filtering AF 0.000982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000828% 10/1,207,252 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00593%	16,870
South Asian	0.00356%	28,062
Remaining individualsnot grpmax-eligible	0.0021%	47,517
European (non-Finnish)	0.000559%	178,842

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.Arg297Gln
Coding: c.890G>A
MANE Select: NM_007220
dbSNP: rs759792043
Type: single nucleotide variant
Location: chrX:15782600 (GRCh38)
Structure: AlphaFold pLDDT 83.33

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-arg297gln (accessed [today's date]).

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