Is CA5B p.Pro50Ala (c.148C>G) pathogenic?

CA5B p.Pro50Ala (c.148C>G) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.3074); Very rare (popmax 0.0094%, nfe).

How common is CA5B p.Pro50Ala (c.148C>G) in the general population?

CA5B p.Pro50Ala (c.148C>G) is very rare (popmax 0.0094%, nfe) (gnomAD).

What do computational predictors say about CA5B p.Pro50Ala (c.148C>G)?

AlphaMissense predicts likely benign (score 0.3074) — an in-silico prediction, not a clinical call.

CA5B p.Pro50Ala

c.148C>G · rs138875072 · VCV2205423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0094%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3074	likely benign
REVEL	0.477	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 15 kb · p 0.28 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.0094% European (non-Finnish) · 84/893,361 alleles

Filtering AF 0.00776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00714%

Overall 0.00722% 87/1,205,724 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0094%	10,635
Admixed American	0.00221%	45,347
Remaining individualsnot grpmax-eligible	0.00211%	47,432
African / African-American	0.00176%	56,708

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.Pro50Ala
Coding: c.148C>G
MANE Select: NM_007220
dbSNP: rs138875072
Type: single nucleotide variant
Location: chrX:15764583 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 50: 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-pro50ala (accessed [today's date]).

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