Is AGTPBP1 p.Phe751Cys (c.2252T>G) pathogenic?

AGTPBP1 p.Phe751Cys (c.2252T>G) is classified Uncertain significance in AGTPBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.9656); Very rare (popmax 0.000657%); Associated with Inborn genetic diseases.

What condition is associated with AGTPBP1 p.Phe751Cys (c.2252T>G)?

AGTPBP1 p.Phe751Cys (c.2252T>G) is associated with Inborn genetic diseases (ClinVar).

How common is AGTPBP1 p.Phe751Cys (c.2252T>G) in the general population?

AGTPBP1 p.Phe751Cys (c.2252T>G) is very rare (popmax 0.000657%) (gnomAD).

What do computational predictors say about AGTPBP1 p.Phe751Cys (c.2252T>G)?

AlphaMissense predicts likely pathogenic (score 0.9656) — an in-silico prediction, not a clinical call.

AGTPBP1 p.Phe751Cys

c.2252T>G · rs928290807 · VCV3097284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9656 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000657%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9656	likely pathogenic
REVEL	0.73	pathogenic-leaning
SaProt	LLR -13.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 74 kb · p 7.5e-11 · regional, not allelic
Overall
CADD	29.8	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 0.000657%

Overall 0.000657% 1/152,214 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.Phe751Cys
Coding: c.2252T>G
MANE Select: NM_001330701
dbSNP: rs928290807
Type: single nucleotide variant
Location: chr9:85619066 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.95
Residue 751: a UniProt-annotated variant site (in condca)

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-phe751cys (accessed [today's date]).

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