Is ACE p.Arg1279Pro (c.3836G>C) pathogenic?

ACE p.Arg1279Pro (c.3836G>C) is classified Uncertain significance in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-04). AlphaMissense: ambiguous (0.5188); Very rare (popmax 0.00824%, sas); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Arg1279Pro (c.3836G>C)?

ACE p.Arg1279Pro (c.3836G>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.Arg1279Pro (c.3836G>C) in the general population?

ACE p.Arg1279Pro (c.3836G>C) is very rare (popmax 0.00824%, sas) (gnomAD).

What do computational predictors say about ACE p.Arg1279Pro (c.3836G>C)?

AlphaMissense predicts ambiguous (score 0.5188) — an in-silico prediction, not a clinical call.

ACE p.Arg1279Pro

c.3836G>C · VCV3582591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00824%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.5188	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -13.54	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.45, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	23.0	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 0.00824% South Asian · 7/84,966 alleles

Filtering AF 0.00382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00269%

Overall 0.000578% 9/1,557,886 alleles · very rare exomes 9/1,405,626 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00824%	12,138
European (non-Finnish)	0.000173%	576,602

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.Arg1279Pro
Coding: c.3836G>C
MANE Select: NM_000789
Type: single nucleotide variant
Location: chr17:63497281 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1279: 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 p.Arg1279Gln Benign/Likely benign ★★ same residue
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

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-arg1279pro (accessed [today's date]).

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