Is ACE2 p.Thr52Ser (c.155C>G) pathogenic?

ACE2 p.Thr52Ser (c.155C>G) is classified Uncertain significance in ACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely benign (0.1449); Very rare (popmax 0.000165%).

How common is ACE2 p.Thr52Ser (c.155C>G) in the general population?

ACE2 p.Thr52Ser (c.155C>G) is very rare (popmax 0.000165%) (gnomAD).

What do computational predictors say about ACE2 p.Thr52Ser (c.155C>G)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

ACE2 p.Thr52Ser

c.155C>G · rs2519715048 · VCV2300427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000165%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -7.73	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 7.5	GERP 0.68, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 39 kb · p 0.0023 · regional, not allelic
Overall
CADD	23.0	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 0.000165%

Overall 0.000165% 2/1,210,987 alleles · very rare exomes 2/1,097,346 · genomes 0/113,641 · joint denominator

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: ACE2
Protein: p.Thr52Ser
Coding: c.155C>G
MANE Select: NM_001371415
dbSNP: rs2519715048
Type: single nucleotide variant
Location: chrX:15600757 (GRCh38)
Structure: AlphaFold pLDDT 91.13 · 328 PDB
Residue 52: an α-helix; the peptidase m2 domain

Full ACE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACE2 c.584-7C>A Likely benign ★★ same type
ACE2 p.Asn690= Benign ★★ same type
ACE2 p.Lys26Arg Likely benign ★★ same type
BMX p.Ala214Val Benign ★★ same type
ACE2 c.2309+2T>A Uncertain significance ★ same type
ACE2 p.Arg161Lys Uncertain significance ★ ⚠ same type
ACE2 p.Asn277Asp Uncertain significance ★ ⚠ same type
ACE2 p.Asn682Ser Uncertain significance ★ ⚠ 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/ace2-p-thr52ser (accessed [today's date]).

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