Is ACE2 p.Arg161Lys (c.482G>A) pathogenic?

ACE2 p.Arg161Lys (c.482G>A) is classified Uncertain significance in ACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: likely benign (0.191); Absent from gnomAD v4.1.

How common is ACE2 p.Arg161Lys (c.482G>A) in the general population?

ACE2 p.Arg161Lys (c.482G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACE2 p.Arg161Lys (c.482G>A)?

AlphaMissense predicts likely benign (score 0.191) — an in-silico prediction, not a clinical call.

ACE2 p.Arg161Lys

c.482G>A · rs2519704915 · VCV2266711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.191 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.191	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 39 kb · p 0.0023 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACE2
Protein: p.Arg161Lys
Coding: c.482G>A
MANE Select: NM_001371415
dbSNP: rs2519704915
Type: single nucleotide variant
Location: chrX:15591814 (GRCh38)
Structure: AlphaFold pLDDT 91.13 · 328 PDB
Residue 161: 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.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-arg161lys (accessed [today's date]).

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