Is ACE p.Pro202Leu (c.605C>T) pathogenic?

ACE p.Pro202Leu (c.605C>T) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1017); Rare (popmax 0.428%, afr).

How common is ACE p.Pro202Leu (c.605C>T) in the general population?

ACE p.Pro202Leu (c.605C>T) is rare (popmax 0.428%, afr) (gnomAD).

What do computational predictors say about ACE p.Pro202Leu (c.605C>T)?

AlphaMissense predicts likely benign (score 0.1017) — an in-silico prediction, not a clinical call.

ACE p.Pro202Leu

c.605C>T · rs148460287 · VCV2042884

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1017 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.428%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1017	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -11.88	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 3.2	GERP 1.2, phastCons 0.93
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	22.8	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 0.428% African / African-American · 321/75,048 alleles

Filtering AF 0.389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.374%

Overall 0.0247% 398/1,612,868 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.428%	234
Remaining individualsnot grpmax-eligible	0.0256%	3,906
East Asian	0.0245%	4,081
European (non-Finnish)	0.00398%	25,107
Admixed American	0.00333%	30,013
South Asian	0.0011%	91,088

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.Pro202Leu
Coding: c.605C>T
MANE Select: NM_000789
dbSNP: rs148460287
Type: single nucleotide variant
Location: chr17:63479862 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 202: an α-helix; 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-pro202leu (accessed [today's date]).

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