Is TMPO p.Gln432= (c.1296A>G) pathogenic?

TMPO p.Gln432= (c.1296A>G) is classified Likely benign in TMPO (ClinVar, Multiple submitters, 4 submitters; last evaluated 2020-01-14). Rare (popmax 0.245%, afr).

How common is TMPO p.Gln432= (c.1296A>G) in the general population?

TMPO p.Gln432= (c.1296A>G) is rare (popmax 0.245%, afr) (gnomAD).

TMPO p.Gln432=

c.1296A>G · rs61744201 · VCV1196339

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.245%, afr)

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 6.2	GERP 2.7, phastCons 1
Overall
CADD	9.501	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.245% African / African-American · 184/75,032 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0134% 216/1,614,106 alleles · rare exomes 109/1,461,808 · genomes 107/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.245%	408
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.0183%	5,454
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,529
European (non-Finnish)	0.000254%	393,343

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: TMPO
Protein: p.Gln432=
Coding: c.1296A>G
MANE Select: NM_001032283
dbSNP: rs61744201
Type: single nucleotide variant
Location: chr12:98547789 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB

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

Similar variants

TMPO c.565+1005A>G Uncertain significance ★★ ⚠ same type
TMPO c.565+1009T>C Uncertain significance ★★ ⚠ same type
TMPO c.565+1012A>C Uncertain significance ★★ ⚠ same type
TMPO c.565+1017A>G Uncertain significance ★★ ⚠ same type
TMPO c.565+1026A>G Uncertain significance ★★ ⚠ same type
TMPO c.565+1029G>T Uncertain significance ★★ ⚠ same type
TMPO c.565+1048G>C Uncertain significance ★★ ⚠ same type
TMPO c.565+1053A>G 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/tmpo-p-gln432 (accessed [today's date]).

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