Is ACE p.His71Gln (c.213C>A) pathogenic?

ACE p.His71Gln (c.213C>A) is classified Uncertain significance in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-06). AlphaMissense: likely benign (0.303); Very rare (popmax 0.00233%, amr).

How common is ACE p.His71Gln (c.213C>A) in the general population?

ACE p.His71Gln (c.213C>A) is very rare (popmax 0.00233%, amr) (gnomAD).

What do computational predictors say about ACE p.His71Gln (c.213C>A)?

AlphaMissense predicts likely benign (score 0.303) — an in-silico prediction, not a clinical call.

ACE p.His71Gln

c.213C>A · rs766548114 · VCV1942620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.303 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.303	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -8.36	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 -0.25	GERP -2.4, phastCons 0.034
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00233% Admixed American · 1/42,994 alleles

Overall 0.00021% 3/1,431,902 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00233%	42,994
African / African-American	0.00149%	67,306
European (non-Finnish)	9.21e-05%	1,086,202

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.His71Gln
Coding: c.213C>A
MANE Select: NM_000789
dbSNP: rs766548114
Type: single nucleotide variant
Location: chr17:63477307 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 71: 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 p.His71Tyr Likely benign ★ same residue
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

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-his71gln (accessed [today's date]).

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