Is ACE p.Val1069Ile (c.3205G>A) pathogenic?

ACE p.Val1069Ile (c.3205G>A) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-12). AlphaMissense: likely benign (0.0795); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACE p.Val1069Ile (c.3205G>A)?

ACE p.Val1069Ile (c.3205G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACE p.Val1069Ile (c.3205G>A) in the general population?

ACE p.Val1069Ile (c.3205G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ACE p.Val1069Ile (c.3205G>A)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

ACE p.Val1069Ile

c.3205G>A · rs147763588 · VCV2054562

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -7.37	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 -0.29	GERP -3.6
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	6.284	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 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000867% 14/1,613,930 alleles · very rare exomes 10/1,461,892 · genomes 4/152,038 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,445
African / African-American	0.00401%	24,951
Remaining individualsnot grpmax-eligible	0.0016%	62,490
Finnishnot grpmax-eligible	0.00156%	63,998
South Asian	0.0011%	91,084
European (non-Finnish)	0.000508%	196,672

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.Val1069Ile
Coding: c.3205G>A
MANE Select: NM_000789
dbSNP: rs147763588
Type: single nucleotide variant
Location: chr17:63493990 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1069: an α-helix; the peptidase m2 2 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.Lys601Arg 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-val1069ile (accessed [today's date]).

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