Is CA5B p.Gly271Arg (c.811G>A) pathogenic?

CA5B p.Gly271Arg (c.811G>A) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.3911); Very rare (popmax 0.00067%, nfe).

How common is CA5B p.Gly271Arg (c.811G>A) in the general population?

CA5B p.Gly271Arg (c.811G>A) is very rare (popmax 0.00067%, nfe) (gnomAD).

What do computational predictors say about CA5B p.Gly271Arg (c.811G>A)?

AlphaMissense predicts ambiguous (score 0.3911) — an in-silico prediction, not a clinical call.

CA5B p.Gly271Arg

c.811G>A · rs1932042581 · VCV2307242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00067%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3911	ambiguous
REVEL	0.577	indeterminate
SaProt	LLR -9.26	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 18 kb · p 0.53 · regional, not allelic
Overall
CADD	25.5	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 0.00067% European (non-Finnish) · 6/894,983 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000547% 6/1,097,490 alleles · very rare

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.Gly271Arg
Coding: c.811G>A
MANE Select: NM_007220
dbSNP: rs1932042581
Type: single nucleotide variant
Location: chrX:15782521 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 271: 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-gly271arg (accessed [today's date]).

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