Is ACE p.Ala154Thr (c.460G>A) pathogenic?

ACE p.Ala154Thr (c.460G>A) is classified Benign in ACE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0837); Rare (popmax 0.774%, eas); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Ala154Thr (c.460G>A)?

ACE p.Ala154Thr (c.460G>A) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Ala154Thr (c.460G>A) in the general population?

ACE p.Ala154Thr (c.460G>A) is rare (popmax 0.774%, eas) (gnomAD).

What do computational predictors say about ACE p.Ala154Thr (c.460G>A)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

ACE p.Ala154Thr

c.460G>A · rs13306087 · VCV892185

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.774%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.5, phastCons 0.95
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	18.56	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 0.774% East Asian · 347/44,812 alleles

Filtering AF 0.707% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.681%

Overall 0.0304% 491/1,613,538 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.774%	129
Remaining individualsnot grpmax-eligible	0.125%	801
African / African-American	0.036%	2,774
South Asian	0.0132%	7,582
Admixed American	0.0117%	8,568
Finnishnot grpmax-eligible	0.00313%	31,972
European (non-Finnish)	0.00153%	65,548

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.Ala154Thr
Coding: c.460G>A
MANE Select: NM_000789
dbSNP: rs13306087
Type: single nucleotide variant
Location: chr17:63479049 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 154: a UniProt-annotated variant site (in); the peptidase m2 1 domain

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

Disease context

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

Similar variants

ACE p.Ala154Val Uncertain significance ★ ⚠ same residue
ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same condition
ACE c.3503+1G>C Likely pathogenic ★★ same condition
ACE p.Arg496Ter Pathogenic/Likely pathogenic ★★ same condition
ACE p.Arg508Ter Pathogenic ★★ same condition
ACE p.Arg791Ter Pathogenic ★★ same condition
ACE p.Tyr266Ter Pathogenic/Likely pathogenic ★★ same condition
ACE c.2739+5G>A Uncertain significance ★★ 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-ala154thr (accessed [today's date]).

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