Is CA4 p.Glu211= (c.633G>A) pathogenic?

CA4 p.Glu211= (c.633G>A) is classified Likely benign in CA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Very rare (popmax 0.00891%, eas).

How common is CA4 p.Glu211= (c.633G>A) in the general population?

CA4 p.Glu211= (c.633G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

CA4 p.Glu211=

c.633G>A · rs376618460 · VCV1935218

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.32, phastCons 0.99
Overall
CADD	7.646	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,890 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000434% 7/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
Admixed American	0.00167%	60,002
European (non-Finnish)	0.000169%	590,023

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.Glu211=
Coding: c.633G>A
MANE Select: NM_000717
dbSNP: rs376618460
Type: single nucleotide variant
Location: chr17:60158335 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.86 · 10 PDB
Residue 211: a disulfide bond; the alpha-carbonic anhydrase domain; an α-helix

Full CA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA4 p.Glu211Val 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-glu211 (accessed [today's date]).

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