Is AGTPBP1 p.Ile252Val (c.754A>G) pathogenic?

AGTPBP1 p.Ile252Val (c.754A>G) is classified Uncertain significance in AGTPBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0709); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGTPBP1 p.Ile252Val (c.754A>G)?

AGTPBP1 p.Ile252Val (c.754A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AGTPBP1 p.Ile252Val (c.754A>G) in the general population?

AGTPBP1 p.Ile252Val (c.754A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AGTPBP1 p.Ile252Val (c.754A>G)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

AGTPBP1 p.Ile252Val

c.754A>G · VCV4572906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.5	GERP 0.68, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 91 kb · p 0.015 · regional, not allelic
Overall
CADD	16.84	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 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.84e-05% 1/1,461,698 alleles · very rare

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: AGTPBP1
Protein: p.Ile252Val
Coding: c.754A>G
MANE Select: NM_001330701
Type: single nucleotide variant
Location: chr9:85657590 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.95

Full AGTPBP1 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

AGTPBP1 p.Ala461Gly Uncertain significance ★★ ⚠ same condition
AGTPBP1 p.Arg1136His Uncertain significance ★★ ⚠ same condition
AGTPBP1 p.Glu1176Gly Uncertain significance ★★ ⚠ same condition
AGTPBP1 p.Ala1065Thr Uncertain significance ★ ⚠ same condition
AGTPBP1 p.Ala140Thr Uncertain significance ★ ⚠ same condition
AGTPBP1 p.Arg1008His Uncertain significance ★ ⚠ same condition
AGTPBP1 p.Arg100Gln Uncertain significance ★ ⚠ same condition
AGTPBP1 p.Arg1086Cys 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/agtpbp1-p-ile252val (accessed [today's date]).

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