Is ACE2 p.Asn690= (c.2070T>C) pathogenic?

ACE2 p.Asn690= (c.2070T>C) is classified Benign in ACE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-30). Common (popmax 6.38%, afr) — too common for a highly-penetrant pathogenic allele.

ACE2 p.Asn690=

Q: How common is ACE2 p.Asn690= (c.2070T>C) in the general population?

ACE2 p.Asn690= (c.2070T>C) is common (popmax 6.38%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2070T>C · rs4646179 · VCV778980

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.38%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.67	GERP -2.9
Overall
CADD	0.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.38% African / African-American · 3,640/57,041 alleles

Filtering AF 6.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.14%

Overall 0.377% 4,561/1,209,518 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.38%	16
Ashkenazi Jewishnot grpmax-eligible	0.686%	146
Middle Eastern	0.598%	167
Remaining individualsnot grpmax-eligible	0.458%	218
Admixed American	0.455%	220
European (non-Finnish)	0.0336%	2,973
South Asian	0.03%	3,338

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.Asn690=
Coding: c.2070T>C
MANE Select: NM_001371415
dbSNP: rs4646179
Type: single nucleotide variant
Location: chrX:15566297 (GRCh38)
Structure: AlphaFold pLDDT 91.13 · 328 PDB
Residue 690: a turn; the collectrin-like 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.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
ACE2 p.Asn712Tyr 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-asn690 (accessed [today's date]).

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