Is ACE2 p.Glu231= (c.693A>G) pathogenic?

ACE2 p.Glu231= (c.693A>G) is classified Likely benign in ACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Very rare (popmax 0.000112%, nfe).

How common is ACE2 p.Glu231= (c.693A>G) in the general population?

ACE2 p.Glu231= (c.693A>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

ACE2 p.Glu231=

c.693A>G · rs2519701547 · VCV2660057

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 1	GERP -0.76, phastCons 0.51
Overall
CADD	2.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/892,884 alleles

Overall 9.13e-05% 1/1,095,039 alleles · very rare

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: ACE2
Protein: p.Glu231=
Coding: c.693A>G
MANE Select: NM_001371415
dbSNP: rs2519701547
Type: single nucleotide variant
Location: chrX:15589347 (GRCh38)
Structure: AlphaFold pLDDT 91.13 · 328 PDB
Residue 231: an α-helix; the peptidase m2 domain

Full ACE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACE2 c.584-7C>A Likely benign ★★ same type
ACE2 p.Asn690= Benign ★★ same type
ACE2 p.Lys26Arg Likely benign ★★ same type
BMX p.Ala214Val Benign ★★ same type
ACE2 c.2309+2T>A Uncertain significance ★ same type
ACE2 p.Arg161Lys Uncertain significance ★ ⚠ same type
ACE2 p.Asn277Asp Uncertain significance ★ ⚠ same type
ACE2 p.Asn682Ser 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/ace2-p-glu231 (accessed [today's date]).

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