Is ACE2 p.Asp367= (c.1101C>T) pathogenic?

ACE2 p.Asp367= (c.1101C>T) is classified Likely benign in ACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Very rare (popmax 0.00528%, sas).

How common is ACE2 p.Asp367= (c.1101C>T) in the general population?

ACE2 p.Asp367= (c.1101C>T) is very rare (popmax 0.00528%, sas) (gnomAD).

ACE2 p.Asp367=

c.1101C>T · rs750477605 · VCV2660056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00528%, sas)

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 0.16	GERP -3.7, phastCons 0.44
Overall
CADD	4.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00528% South Asian · 3/56,775 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.00108% 13/1,208,479 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00528%	18,925
East Asian	0.00296%	33,765
Remaining individualsnot grpmax-eligible	0.0021%	47,556
African / African-American	0.00175%	57,147
European (non-Finnish)	0.000783%	127,736

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.Asp367=
Coding: c.1101C>T
MANE Select: NM_001371415
dbSNP: rs750477605
Type: single nucleotide variant
Location: chrX:15578285 (GRCh38)
Structure: AlphaFold pLDDT 91.13 · 328 PDB
Residue 367: 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-asp367 (accessed [today's date]).

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