Is AGK p.Arg9Gly (c.25C>G) pathogenic?

AGK p.Arg9Gly (c.25C>G) is classified Uncertain significance in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely pathogenic (0.5681); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Arg9Gly (c.25C>G)?

AGK p.Arg9Gly (c.25C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AGK p.Arg9Gly (c.25C>G) in the general population?

AGK p.Arg9Gly (c.25C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AGK p.Arg9Gly (c.25C>G)?

AlphaMissense predicts likely pathogenic (score 0.5681) — an in-silico prediction, not a clinical call.

AGK p.Arg9Gly

c.25C>G · VCV4251523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5681	likely pathogenic
REVEL	0.356	indeterminate
SaProt	LLR -10.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 3.4, phastCons 1
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,878 alleles

Overall 0.000137% 2/1,461,720 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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: AGK
Protein: p.Arg9Gly
Coding: c.25C>G
MANE Select: NM_018238
Type: single nucleotide variant
Location: chr7:141555491 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGK p.Arg9Pro Uncertain significance ★★ ⚠ same residue
AGK p.Arg9Ter Pathogenic ★ same residue
AGK p.Arg9= Uncertain significance ★ same residue
AGK p.Arg9Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AGK c.424-3C>G Pathogenic/Likely pathogenic ★★ same condition
AGK p.Arg138Ter Pathogenic ★★ same condition
AGK p.Ala42Pro Uncertain significance ★★ ⚠ same condition
AGK p.Ala71Val 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/agk-p-arg9gly (accessed [today's date]).

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