Is ACE p.Lys601Arg (c.1802A>G) pathogenic?

ACE p.Lys601Arg (c.1802A>G) is classified Uncertain significance in ACE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.0179%, mid); Associated with Inborn genetic diseases.

What condition is associated with ACE p.Lys601Arg (c.1802A>G)?

ACE p.Lys601Arg (c.1802A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACE p.Lys601Arg (c.1802A>G) in the general population?

ACE p.Lys601Arg (c.1802A>G) is ultra-rare (popmax 0.0179%, mid) (gnomAD).

What do computational predictors say about ACE p.Lys601Arg (c.1802A>G)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

ACE p.Lys601Arg

c.1802A>G · rs776418026 · VCV1985393

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -4.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.13	GERP -0.48
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	12.67	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

Grpmax group 0.0179% Middle Eastern · 1/5,592 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00143% 23/1,612,334 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0179%	5,592
South Asian	0.0154%	6,493
African / African-American	0.00267%	37,463
Remaining individualsnot grpmax-eligible	0.0016%	62,390
European (non-Finnish)	0.000424%	235,988

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: ACE
Protein: p.Lys601Arg
Coding: c.1802A>G
MANE Select: NM_000789
dbSNP: rs776418026
Type: single nucleotide variant
Location: chr17:63484422 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 601: an α-helix; the peptidase m2 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACE p.Ala225Ser Uncertain significance ★★ ⚠ same condition
ACE p.Ala361Thr Uncertain significance ★★ ⚠ same condition
ACE p.Arg814Gln Uncertain significance ★★ ⚠ same condition
ACE p.Asn671Ser Uncertain significance ★★ ⚠ same condition
ACE p.Asp746Asn Uncertain significance ★★ ⚠ same condition
ACE p.Gln25Leu Uncertain significance ★★ ⚠ same condition
ACE p.Glu638Lys Uncertain significance ★★ ⚠ same condition
ACE p.Ser1195Leu Uncertain significance ★★ ⚠ same condition

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/ace-p-lys601arg (accessed [today's date]).

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