Is ACE p.Ser1121= (c.3363T>C) pathogenic?

ACE p.Ser1121= (c.3363T>C) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-18). Rare (popmax 0.553%, eas); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Ser1121= (c.3363T>C)?

ACE p.Ser1121= (c.3363T>C) is associated with renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis (ClinVar).

How common is ACE p.Ser1121= (c.3363T>C) in the general population?

ACE p.Ser1121= (c.3363T>C) is rare (popmax 0.553%, eas) (gnomAD).

ACE p.Ser1121=

c.3363T>C · rs200201337 · VCV889650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.553%, eas)

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.18	GERP -3.4, phastCons 0.28
Overall
CADD	5.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.553% East Asian · 248/44,884 alleles

Filtering AF 0.496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.474%

Overall 0.0206% 333/1,613,984 alleles · rare exomes 272/1,461,646 · genomes 61/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.553%	181
Remaining individualsnot grpmax-eligible	0.101%	992
Admixed American	0.0183%	5,454
African / African-American	0.00933%	10,722
European (non-Finnish)	0.000339%	294,986

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.Ser1121=
Coding: c.3363T>C
MANE Select: NM_000789
dbSNP: rs200201337
Type: single nucleotide variant
Location: chr17:63494453 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1121: a turn; the peptidase m2 2 domain

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 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-ser1121 (accessed [today's date]).

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