Is HOXB13 p.Pro110= (c.330C>A) pathogenic?

HOXB13 p.Pro110= (c.330C>A) is classified Benign/Likely benign in HOXB13 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.09%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with HOXB13 p.Pro110= (c.330C>A)?

HOXB13 p.Pro110= (c.330C>A) is associated with hereditary neoplastic syndrome, prostate cancer, hereditary, 9 (ClinVar).

How common is HOXB13 p.Pro110= (c.330C>A) in the general population?

HOXB13 p.Pro110= (c.330C>A) is low-frequency (popmax 2.09%, afr) (gnomAD).

HOXB13 p.Pro110=

c.330C>A · rs33993186 · VCV480872

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, afr)

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 0.88	GERP -4.5, phastCons 0.12
Overall
CADD	4.681	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% African / African-American · 1,570/75,062 alleles

Filtering AF 2.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.97%

Overall 0.154% 2,486/1,614,186 alleles · low-frequency exomes 1,511/1,461,852 · genomes 975/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.09%	48
Ashkenazi Jewishnot grpmax-eligible	1.41%	71
Middle Eastern	0.478%	209
Remaining individualsnot grpmax-eligible	0.229%	437
Admixed American	0.195%	513
European (non-Finnish)	0.0173%	5,785
South Asian	0.00659%	15,180
Finnishnot grpmax-eligible	0.00156%	64,014

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.Pro110=
Coding: c.330C>A
MANE Select: NM_006361
dbSNP: rs33993186
Type: single nucleotide variant
Location: chr17:48728264 (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, 9

Similar variants

HOXB13 p.Pro110Ala Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro110Leu Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro110Thr Uncertain significance ★★ ⚠ same residue
HOXB13 p.Pro110Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro110 (accessed [today's date]).

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