Is HOXB13 p.Pro44= (c.132T>C) pathogenic?

HOXB13 p.Pro44= (c.132T>C) is classified Likely benign in HOXB13 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-23). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with HOXB13 p.Pro44= (c.132T>C)?

HOXB13 p.Pro44= (c.132T>C) is associated with hereditary neoplastic syndrome, prostate cancer, hereditary, 1 (ClinVar).

How common is HOXB13 p.Pro44= (c.132T>C) in the general population?

HOXB13 p.Pro44= (c.132T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

HOXB13 p.Pro44=

c.132T>C · rs1597935042 · VCV690492

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

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 -4	GERP -4.6
Overall
CADD	4.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Overall 6.85e-05% 1/1,460,882 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: HOXB13
Protein: p.Pro44=
Coding: c.132T>C
MANE Select: NM_006361
dbSNP: rs1597935042
Type: single nucleotide variant
Location: chr17:48728462 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.34 · 10 PDB

Full HOXB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: prostate cancer, hereditary, 1

Similar variants

HOXB13 p.Pro44Leu Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro44Ser Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro44Thr Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro44Arg Uncertain significance ⚠ same residue
HOXB13 c.601+1G>T Uncertain significance ★★ same condition
HOXB13 c.601+2T>C Uncertain significance ★★ same condition
HOXB13 c.601+4C>T Uncertain significance ★★ same condition
HOXB13 c.602-3C>A 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/hoxb13-p-pro44 (accessed [today's date]).

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