Is ACE p.Arg324Trp (c.970C>T) pathogenic?

ACE p.Arg324Trp (c.970C>T) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.1224); Low-frequency (popmax 2.49%, afr); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Arg324Trp (c.970C>T)?

ACE p.Arg324Trp (c.970C>T) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Arg324Trp (c.970C>T) in the general population?

ACE p.Arg324Trp (c.970C>T) is low-frequency (popmax 2.49%, afr) (gnomAD).

What do computational predictors say about ACE p.Arg324Trp (c.970C>T)?

AlphaMissense predicts likely benign (score 0.1224) — an in-silico prediction, not a clinical call.

ACE p.Arg324Trp

c.970C>T · rs35141294 · VCV324372

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1224 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.49%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.1224	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -10.36	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 2.7	GERP -0.56, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	31.0	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 2.49% African / African-American · 1,869/75,044 alleles

Filtering AF 2.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.156% 2,513/1,613,962 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.49%	40
Middle Eastern	0.462%	216
Admixed American	0.3%	333
Remaining individualsnot grpmax-eligible	0.259%	386
European (non-Finnish)	0.0218%	4,592
South Asian	0.0165%	6,072
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Finnishnot grpmax-eligible	0.00157%	63,842

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.Arg324Trp
Coding: c.970C>T
MANE Select: NM_000789
dbSNP: rs35141294
Type: single nucleotide variant
Location: chr17:63481590 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 324: an α-helix; 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.Arg324Gln 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-arg324trp (accessed [today's date]).

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