Is CA5B p.Cys34Trp (c.102C>G) pathogenic?

CA5B p.Cys34Trp (c.102C>G) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely pathogenic (0.9281); Ultra-rare (popmax 0.0162%, nfe).

How common is CA5B p.Cys34Trp (c.102C>G) in the general population?

CA5B p.Cys34Trp (c.102C>G) is ultra-rare (popmax 0.0162%, nfe) (gnomAD).

What do computational predictors say about CA5B p.Cys34Trp (c.102C>G)?

AlphaMissense predicts likely pathogenic (score 0.9281) — an in-silico prediction, not a clinical call.

CA5B p.Cys34Trp

c.102C>G · rs759916192 · VCV2382608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9281 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9281	likely pathogenic
REVEL	0.549	indeterminate
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP -0.076, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 15 kb · p 0.28 · regional, not allelic
Overall
CADD	23.8	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 0.0162% European (non-Finnish) · 145/895,023 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.0126% 152/1,209,945 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0162%	6,173
Remaining individualsnot grpmax-eligible	0.0105%	9,518
African / African-American	0.00349%	28,620

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.Cys34Trp
Coding: c.102C>G
MANE Select: NM_007220
dbSNP: rs759916192
Type: single nucleotide variant
Location: chrX:15750125 (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-cys34trp (accessed [today's date]).

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