Is AGTPBP1 p.Pro649= (c.1947C>T) pathogenic?

AGTPBP1 p.Pro649= (c.1947C>T) is classified Likely benign in AGTPBP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Ultra-rare (popmax 0.0384%, amr); Associated with AGTPBP1-related disorder.

What condition is associated with AGTPBP1 p.Pro649= (c.1947C>T)?

AGTPBP1 p.Pro649= (c.1947C>T) is associated with AGTPBP1-related disorder (ClinVar).

How common is AGTPBP1 p.Pro649= (c.1947C>T) in the general population?

AGTPBP1 p.Pro649= (c.1947C>T) is ultra-rare (popmax 0.0384%, amr) (gnomAD).

AGTPBP1 p.Pro649=

c.1947C>T · rs376158351 · VCV3040871

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, amr)

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 0.83	GERP -4.1, phastCons 0.97
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% Admixed American · 23/59,964 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00341% 55/1,613,824 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0384%	2,607
East Asian	0.0156%	6,411
African / African-American	0.00534%	18,715
Remaining individualsnot grpmax-eligible	0.0048%	20,826
South Asian	0.0022%	45,533
European (non-Finnish)	0.00136%	73,748

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.Pro649=
Coding: c.1947C>T
MANE Select: NM_001330701
dbSNP: rs376158351
Type: single nucleotide variant
Location: chr9:85632730 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.95
Residue 649: 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.Lys451= 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-pro649 (accessed [today's date]).

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