Is ACE2 p.Lys26Arg (c.77A>G) pathogenic?

ACE2 p.Lys26Arg (c.77A>G) is classified Likely benign in ACE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-08). AlphaMissense: likely benign (0.0765); Rare (popmax 0.665%, nfe).

How common is ACE2 p.Lys26Arg (c.77A>G) in the general population?

ACE2 p.Lys26Arg (c.77A>G) is rare (popmax 0.665%, nfe) (gnomAD).

What do computational predictors say about ACE2 p.Lys26Arg (c.77A>G)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

ACE2 p.Lys26Arg

c.77A>G · rs4646116 · VCV780203

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.665%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -6.15	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 -0.088	GERP -3.1, phastCons 0.001
Regional constraint	o/e 0.87	unconstrained · MANE · 39 kb · p 0.0023 · regional, not allelic
Overall
CADD	0.23	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.665% European (non-Finnish) · 5,950/895,074 alleles

Filtering AF 0.651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.645%

Overall 0.564% 6,821/1,209,853 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.37%	73
European (non-Finnish)grpmax	0.665%	150
Remaining individualsnot grpmax-eligible	0.456%	219
Admixed American	0.35%	286
South Asian	0.169%	591
African / African-American	0.105%	953
Finnishnot grpmax-eligible	0.0729%	1,371
Middle Eastern	0.0689%	1,451

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys26Arg
Coding: c.77A>G
MANE Select: NM_001371415
dbSNP: rs4646116
Type: single nucleotide variant
Location: chrX:15600835 (GRCh38)
Structure: AlphaFold pLDDT 91.13 · 328 PDB
Residue 26: an α-helix; a UniProt-annotated variant site (in); 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
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-lys26arg (accessed [today's date]).

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