Is ACE p.Gly2Val (c.5G>T) pathogenic?

ACE p.Gly2Val (c.5G>T) is classified Benign in ACE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-23). AlphaMissense: ambiguous (0.3682); Low-frequency (popmax 1.38%, afr); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Gly2Val (c.5G>T)?

ACE p.Gly2Val (c.5G>T) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Gly2Val (c.5G>T) in the general population?

ACE p.Gly2Val (c.5G>T) is low-frequency (popmax 1.38%, afr) (gnomAD).

What do computational predictors say about ACE p.Gly2Val (c.5G>T)?

AlphaMissense predicts ambiguous (score 0.3682) — an in-silico prediction, not a clinical call.

ACE p.Gly2Val

c.5G>T · rs558593002 · VCV324357

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3682 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.3682	ambiguous
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.93, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	22.0	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 1.38% African / African-American · 882/64,068 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.27%

Overall 0.077% 1,008/1,309,736 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.38%	73
Middle Eastern	0.146%	686
Admixed American	0.131%	763
Remaining individualsnot grpmax-eligible	0.118%	847
East Asian	0.071%	1,408
European (non-Finnish)	0.000965%	103,633

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.Gly2Val
Coding: c.5G>T
MANE Select: NM_000789
dbSNP: rs558593002
Type: single nucleotide variant
Location: chr17:63477099 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB

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.Gly2Glu 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-gly2val (accessed [today's date]).

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