Is KLK3 p.Pro233= (c.699A>G) pathogenic?

KLK3 p.Pro233= (c.699A>G) is classified Benign in KLK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-22). Low-frequency (popmax 1.42%, afr); Associated with KLK3-related disorder.

What condition is associated with KLK3 p.Pro233= (c.699A>G)?

KLK3 p.Pro233= (c.699A>G) is associated with KLK3-related disorder (ClinVar).

How common is KLK3 p.Pro233= (c.699A>G) in the general population?

KLK3 p.Pro233= (c.699A>G) is low-frequency (popmax 1.42%, afr) (gnomAD).

KLK3 p.Pro233=

c.699A>G · rs79245399 · VCV3039521

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, afr)

Conditions

KLK3-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 -20
Overall
CADD	0.148	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% African / African-American · 1,067/75,044 alleles

Filtering AF 1.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 0.0731% 1,180/1,614,116 alleles · low-frequency exomes 546/1,461,800 · genomes 634/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.42%	70
Admixed American	0.102%	984
Remaining individualsnot grpmax-eligible	0.0656%	1,524
South Asian	0.0011%	91,090
European (non-Finnish)	0.000847%	117,998

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: KLK3
Protein: p.Pro233=
Coding: c.699A>G
MANE Select: NM_001648
dbSNP: rs79245399
Type: single nucleotide variant
Location: chr19:50860040 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.78 · 6 PDB
Residue 233: the peptidase s1 domain; a β-strand

Full KLK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KLK3-related disorder

Similar variants

KLK3 c.47-9C>G Likely benign same condition
KLK3 c.631-424G>A Benign same condition
KLK3 c.631-425C>T Benign same condition
KLK3 p.Ala18= Benign same condition
KLK3 p.Arg125Cys Benign same condition
KLK3 p.Gln39= Benign same condition
KLK3 p.Gly149= Likely benign same condition
KLK3 p.Gly16= Benign 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/klk3-p-pro233 (accessed [today's date]).

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