Is AGK p.Ile252Val (c.754A>G) pathogenic?

AGK p.Ile252Val (c.754A>G) is classified Uncertain significance in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.082); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Ile252Val (c.754A>G)?

AGK p.Ile252Val (c.754A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AGK p.Ile252Val (c.754A>G) in the general population?

AGK p.Ile252Val (c.754A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AGK p.Ile252Val (c.754A>G)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

AGK p.Ile252Val

c.754A>G · rs1339170140 · VCV3095664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.13	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 3.9	GERP 2.5, phastCons 1
Overall
CADD	14.75	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 0.00223% East Asian · 1/44,886 alleles

Overall 0.000124% 2/1,613,792 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
European (non-Finnish)	8.48e-05%	1,179,906

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.Ile252Val
Coding: c.754A>G
MANE Select: NM_018238
dbSNP: rs1339170140
Type: single nucleotide variant
Location: chr7:141641275 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB
Residue 252: the 'disordered' region; a UniProt-annotated variant site (in mtdps10)

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 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
AGK p.Arg137Gln Uncertain significance ★★ ⚠ same condition
AGK p.Arg9Pro Uncertain significance ★★ ⚠ same condition
AGK p.Asn36Lys Uncertain significance ★★ ⚠ same condition
AGK p.Asn68Ser 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-ile252val (accessed [today's date]).

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