Is AGTPBP1 p.Lys451= (c.1353A>G) pathogenic?

AGTPBP1 p.Lys451= (c.1353A>G) is classified Benign in AGTPBP1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-06-17). Low-frequency (popmax 2.36%, sas); Associated with AGTPBP1-related disorder.

What condition is associated with AGTPBP1 p.Lys451= (c.1353A>G)?

AGTPBP1 p.Lys451= (c.1353A>G) is associated with AGTPBP1-related disorder (ClinVar).

How common is AGTPBP1 p.Lys451= (c.1353A>G) in the general population?

AGTPBP1 p.Lys451= (c.1353A>G) is low-frequency (popmax 2.36%, sas) (gnomAD).

AGTPBP1 p.Lys451=

c.1353A>G · rs144890878 · VCV3055657

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.36%, sas)

Conditions

AGTPBP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -3.2, phastCons 0.97
Overall
CADD	7.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.36% South Asian · 2,063/87,270 alleles

Filtering AF 2.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.24%

Overall 0.687% 10,976/1,598,152 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.36%	42
Middle Eastern	2.17%	46
Finnishnot grpmax-eligible	0.942%	106
Amishnot grpmax-eligible	0.877%	114
European (non-Finnish)	0.625%	160
Remaining individualsnot grpmax-eligible	0.616%	162
Admixed American	0.453%	221
Ashkenazi Jewishnot grpmax-eligible	0.359%	279
African / African-American	0.125%	803
East Asian	0.00669%	14,939

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.Lys451=
Coding: c.1353A>G
MANE Select: NM_001330701
dbSNP: rs144890878
Type: single nucleotide variant
Location: chr9:85633324 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.95
Residue 451: a UniProt-annotated variant site (in condca)

Full AGTPBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AGTPBP1-related disorder

Similar variants

AGTPBP1 c.2336-1G>T Pathogenic ★ same condition
AGTPBP1 c.2186+10T>G Benign same condition
AGTPBP1 p.Leu131= Benign same condition
AGTPBP1 p.Pro649= Likely benign same condition
AGTPBP1 p.Thr1084= Likely benign same condition
AGTPBP1 p.Tyr964Terfs Pathogenic ★ same condition
AGTPBP1 c.-179GCC[4] Benign same condition
AGTPBP1 c.-206G>A Uncertain significance ★★ same type

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-lys451 (accessed [today's date]).

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