CA4 p.Glu171=
c.513G>A · rs368617056 · VCV954923
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00892%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.90 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.79 | loss · gain 0.28 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 8.1 | GERP 0.56, phastCons 1 |
| Overall | ||
| CADD | 21.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
European (non-Finnish) · 105/1,177,584 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00702%
Overall
0.00676%
109/1,611,358 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00892% | 11,215 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,195 |
| Finnishnot grpmax-eligible | 0.00156% | 63,978 |
| African / African-American | 0.00134% | 74,902 |
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
- CA4
- Protein
- p.Glu171=
- Coding
- c.513G>A
- MANE Select
- NM_000717
- dbSNP
- rs368617056
- Type
- single nucleotide variant
- Location
- chr17:60157788 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 171
- a disulfide bond; the alpha-carbonic anhydrase domain; a β-strand
Similar variants
- CA4 p.Glu171Lys Uncertain significance ★ ⚠ same residue
- CA4 c.745-9C>G Uncertain significance ★★ same type
- CA4 p.Ala156Val Uncertain significance ★★ ⚠ same type
- CA4 p.Ala308Ser Uncertain significance ★★ ⚠ same type
- CA4 p.Arg279Pro Uncertain significance ★★ ⚠ same type
- CA4 p.Arg50His Uncertain significance ★★ ⚠ same type
- CA4 p.Arg50Ser Uncertain significance ★★ ⚠ same type
- CA4 p.Asp131Asn 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/ca4-p-glu171 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown