Is ACE p.Asp295His (c.883G>C) pathogenic?

ACE p.Asp295His (c.883G>C) is classified Uncertain significance in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). AlphaMissense: likely benign (0.2478); Very rare (popmax 8.49e-05%, nfe); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Asp295His (c.883G>C)?

ACE p.Asp295His (c.883G>C) is associated with renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3, hemorrhage, intracerebral, susceptibility to (ClinVar).

How common is ACE p.Asp295His (c.883G>C) in the general population?

ACE p.Asp295His (c.883G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ACE p.Asp295His (c.883G>C)?

AlphaMissense predicts likely benign (score 0.2478) — an in-silico prediction, not a clinical call.

ACE p.Asp295His

c.883G>C · VCV3582446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2478 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.2478	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -10.64	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.78, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	25.8	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 8.49e-05% European (non-Finnish) · 1/1,178,402 alleles

Overall 6.21e-05% 1/1,610,966 alleles · very rare exomes 0/1,459,138 · genomes 1/151,828 · joint denominator

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.Asp295His
Coding: c.883G>C
MANE Select: NM_000789
Type: single nucleotide variant
Location: chr17:63481126 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 295: an α-helix; 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

Disease context

renal tubular dysgenesis of genetic origin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microvascular complications of diabetes, susceptibility to, 3 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-asp295his (accessed [today's date]).

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