Is ACE p.Asp592Val (c.1775A>T) pathogenic?

ACE p.Asp592Val (c.1775A>T) is classified Uncertain significance in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-25). AlphaMissense: likely benign (0.1691); Very rare (popmax 0.0066%, sas).

How common is ACE p.Asp592Val (c.1775A>T) in the general population?

ACE p.Asp592Val (c.1775A>T) is very rare (popmax 0.0066%, sas) (gnomAD).

What do computational predictors say about ACE p.Asp592Val (c.1775A>T)?

AlphaMissense predicts likely benign (score 0.1691) — an in-silico prediction, not a clinical call.

ACE p.Asp592Val

c.1775A>T · VCV4765667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0066%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1691	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -11.28	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.6	GERP -1.7, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	14.26	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 0.0066% South Asian · 6/90,870 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000434% 7/1,612,004 alleles · very rare exomes 7/1,459,684 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0066%	15,145
Remaining individualsnot grpmax-eligible	0.0016%	62,384

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.Asp592Val
Coding: c.1775A>T
MANE Select: NM_000789
Type: single nucleotide variant
Location: chr17:63484395 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 592: the peptidase m2 1 domain; a UniProt-annotated variant site (in)

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

Similar variants

ACE p.Asp592Gly Benign/Likely benign ★★ same residue
ACE p.Asp592Asn Uncertain significance ★ ⚠ same residue
ACE c.1342+1G>T Likely pathogenic ★★ same type
ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same type
ACE c.3503+1G>C Likely pathogenic ★★ same type
ACE c.945+2T>G Likely pathogenic ★★ same type
ACE p.Arg265Ter Pathogenic ★★ same type
ACE p.Arg496Gln Likely pathogenic ★★ 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/ace-p-asp592val (accessed [today's date]).

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