Is ACE p.Asp353Asn (c.1057G>A) pathogenic?

ACE p.Asp353Asn (c.1057G>A) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.151); Rare (popmax 0.323%, eas).

How common is ACE p.Asp353Asn (c.1057G>A) in the general population?

ACE p.Asp353Asn (c.1057G>A) is rare (popmax 0.323%, eas) (gnomAD).

What do computational predictors say about ACE p.Asp353Asn (c.1057G>A)?

AlphaMissense predicts likely benign (score 0.151) — an in-silico prediction, not a clinical call.

ACE p.Asp353Asn

c.1057G>A · rs148193919 · VCV713533

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.151 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.323%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.151	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -9.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	27.2	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 0.323% East Asian · 145/44,862 alleles

Filtering AF 0.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.264%

Overall 0.0158% 255/1,614,058 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.323%	309
Remaining individualsnot grpmax-eligible	0.0688%	1,454
Finnishnot grpmax-eligible	0.0344%	2,909
South Asian	0.0209%	4,793
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
Admixed American	0.01%	10,003
African / African-American	0.00666%	15,009
European (non-Finnish)	0.000847%	117,999

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.Asp353Asn
Coding: c.1057G>A
MANE Select: NM_000789
dbSNP: rs148193919
Type: single nucleotide variant
Location: chr17:63481677 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 353: a β-strand; the peptidase m2 1 domain

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

Similar variants

ACE c.1342+1G>T Likely pathogenic ★★ same type
ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same type
ACE c.3503+1G>C Likely pathogenic ★★ same type
ACE c.945+2T>G Likely pathogenic ★★ same type
ACE p.Arg265Ter Pathogenic ★★ same type
ACE p.Arg496Gln Likely pathogenic ★★ same type
ACE p.Arg496Ter Pathogenic/Likely pathogenic ★★ same type
ACE p.Arg508Ter Pathogenic ★★ same type

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-asp353asn (accessed [today's date]).

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