Is ACE p.Val773Met (c.2317G>A) pathogenic?

ACE p.Val773Met (c.2317G>A) is classified Uncertain significance in ACE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-30). AlphaMissense: likely benign (0.0845); Ultra-rare (popmax 0.0225%, nfe); Associated with microvascular complications of diabetes, susceptibility to, 3.

What condition is associated with ACE p.Val773Met (c.2317G>A)?

ACE p.Val773Met (c.2317G>A) is associated with microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis of genetic origin, hemorrhage, intracerebral, susceptibility to (ClinVar).

How common is ACE p.Val773Met (c.2317G>A) in the general population?

ACE p.Val773Met (c.2317G>A) is ultra-rare (popmax 0.0225%, nfe) (gnomAD).

What do computational predictors say about ACE p.Val773Met (c.2317G>A)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

ACE p.Val773Met

c.2317G>A · rs143830698 · VCV1514880

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microvascular complications of diabetes, susceptibility to, 3

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.71	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 -0.59	GERP -3.7
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	6.64	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 0.0225% European (non-Finnish) · 265/1,179,894 alleles

Filtering AF 0.0202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.0174% 281/1,613,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0225%	4,452
African / African-American	0.0121%	8,293
Remaining individualsnot grpmax-eligible	0.0064%	15,617
South Asian	0.0033%	30,338

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: ACE
Protein: p.Val773Met
Coding: c.2317G>A
MANE Select: NM_000789
dbSNP: rs143830698
Type: single nucleotide variant
Location: chr17:63488659 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 773: an α-helix; the peptidase m2 2 domain

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

Disease context

microvascular complications of diabetes, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal tubular dysgenesis of genetic origin hemorrhage, intracerebral, susceptibility to

Similar variants

ACE c.1342+1G>T Likely pathogenic ★★ same condition
ACE c.3503+1G>C Likely pathogenic ★★ same condition
ACE c.945+2T>G Likely pathogenic ★★ same condition
ACE p.Arg265Ter Pathogenic ★★ same condition
ACE p.Arg508Ter Pathogenic ★★ same condition
ACE p.Arg791Ter Pathogenic ★★ same condition
ACE p.Gln396Ter Pathogenic/Likely pathogenic ★★ same condition
ACE p.Met1Thr Pathogenic/Likely pathogenic ★★ 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-val773met (accessed [today's date]).

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