Is HOXB13 p.Pro44Arg (c.131C>G) pathogenic?

HOXB13 p.Pro44Arg (c.131C>G) is classified Uncertain significance in HOXB13 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.159); Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with HOXB13 p.Pro44Arg (c.131C>G)?

HOXB13 p.Pro44Arg (c.131C>G) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is HOXB13 p.Pro44Arg (c.131C>G) in the general population?

HOXB13 p.Pro44Arg (c.131C>G) is absent from gnomAD v4.1 (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about HOXB13 p.Pro44Arg (c.131C>G)?

AlphaMissense predicts likely benign (score 0.159) — an in-silico prediction, not a clinical call.

HOXB13 p.Pro44Arg

c.131C>G · rs866159706 · VCV690543

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
AlphaMissense	0.159	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,800 bp · p 0.61 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HOXB13
Protein: p.Pro44Arg
Coding: c.131C>G
MANE Select: NM_006361
dbSNP: rs866159706
Type: single nucleotide variant
Location: chr17:48728463 (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

prostate cancer, hereditary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

HOXB13 p.Pro44= Likely benign ★ same residue
HOXB13 p.Pro44Leu Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro44Ser Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro44Thr Uncertain significance ★★ ⚠ same residue
HOXB13 c.602-3C>A Uncertain significance ★★ same condition
HOXB13 p.Ala212Pro Uncertain significance ★★ ⚠ same condition
HOXB13 p.Ala38Val Uncertain significance ★★ ⚠ same condition
HOXB13 p.Ala39Gly 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-pro44arg (accessed [today's date]).

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