Is ACE p.Asp72Tyr (c.214G>T) pathogenic?

ACE p.Asp72Tyr (c.214G>T) is classified Uncertain significance in ACE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.3403); Very rare (popmax 0.00308%, eas); Associated with microvascular complications of diabetes, susceptibility to, 3.

What condition is associated with ACE p.Asp72Tyr (c.214G>T)?

ACE p.Asp72Tyr (c.214G>T) is associated with microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis of genetic origin, renal tubular dysgenesis (ClinVar).

How common is ACE p.Asp72Tyr (c.214G>T) in the general population?

ACE p.Asp72Tyr (c.214G>T) is very rare (popmax 0.00308%, eas) (gnomAD).

What do computational predictors say about ACE p.Asp72Tyr (c.214G>T)?

AlphaMissense predicts ambiguous (score 0.3403) — an in-silico prediction, not a clinical call.

ACE p.Asp72Tyr

c.214G>T · rs752559637 · VCV890947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00308%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

microvascular complications of diabetes, susceptibility to, 3

Computational evidence

Protein change
AlphaMissense	0.3403	ambiguous
REVEL	0.24	benign-leaning
SaProt	LLR -8.04	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -3.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	17.1	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 0.00308% East Asian · 1/32,490 alleles

Filtering AF 0.000483% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000342%

Overall 0.00106% 15/1,420,388 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00308%	32,490
South Asian	0.00291%	34,329
Admixed American	0.00235%	42,496
African / African-American	0.00148%	67,622
European (non-Finnish)	0.000927%	107,926

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.Asp72Tyr
Coding: c.214G>T
MANE Select: NM_000789
dbSNP: rs752559637
Type: single nucleotide variant
Location: chr17:63477308 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 72: an α-helix; the peptidase m2 1 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 renal tubular dysgenesis hemorrhage, intracerebral, susceptibility to

Similar variants

ACE c.1342+1G>T Likely pathogenic ★★ same condition
ACE c.1709+5G>C Pathogenic/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.Arg496Ter Pathogenic/Likely pathogenic ★★ same condition
ACE p.Arg508Ter Pathogenic ★★ same condition
ACE p.Arg791Ter 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-asp72tyr (accessed [today's date]).

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