Is CA5B p.Pro201Leu (c.602C>T) pathogenic?

CA5B p.Pro201Leu (c.602C>T) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely benign (0.2096); Very rare (popmax 0.00667%, amr).

How common is CA5B p.Pro201Leu (c.602C>T) in the general population?

CA5B p.Pro201Leu (c.602C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CA5B p.Pro201Leu (c.602C>T)?

AlphaMissense predicts likely benign (score 0.2096) — an in-silico prediction, not a clinical call.

CA5B p.Pro201Leu

c.602C>T · rs757565475 · VCV2388712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2096	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 18 kb · p 0.53 · regional, not allelic
Overall
CADD	24.7	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 0.00667% Admixed American · 3/44,951 alleles

Filtering AF 0.00365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00325%

Overall 0.00401% 48/1,196,984 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,984
European (non-Finnish)	0.00485%	20,618
East Asian	0.00298%	33,599
Remaining individualsnot grpmax-eligible	0.00213%	47,025

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.Pro201Leu
Coding: c.602C>T
MANE Select: NM_007220
dbSNP: rs757565475
Type: single nucleotide variant
Location: chrX:15775292 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 201: 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-pro201leu (accessed [today's date]).

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