Is KLK3 p.Ser79= (c.237C>T) pathogenic?

KLK3 p.Ser79= (c.237C>T) is classified Benign in KLK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-12). Common (popmax 19.8%, mid) — too common for a highly-penetrant pathogenic allele; Associated with KLK3-related disorder.

What condition is associated with KLK3 p.Ser79= (c.237C>T)?

KLK3 p.Ser79= (c.237C>T) is associated with KLK3-related disorder (ClinVar).

KLK3 p.Ser79=

Q: How common is KLK3 p.Ser79= (c.237C>T) in the general population?

KLK3 p.Ser79= (c.237C>T) is common (popmax 19.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.237C>T · rs12946 · VCV3057076

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 19.8%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

KLK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6
Overall
CADD	4.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.8% Middle Eastern · 1,200/6,058 alleles

Filtering AF 18.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.5%

Overall 11.9% 191,257/1,613,068 alleles · common exomes 175,196/1,460,862 · genomes 16,061/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	19.8%	5
Ashkenazi Jewishnot grpmax-eligible	19.5%	5
Amishnot grpmax-eligible	17.9%	6
European (non-Finnish)	12.7%	8
Remaining individualsnot grpmax-eligible	12.2%	8
Admixed American	8.88%	11
South Asian	8.65%	12
African / African-American	7.83%	13
East Asian	7.02%	14
Finnishnot grpmax-eligible	6.61%	15

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.Ser79=
Coding: c.237C>T
MANE Select: NM_001648
dbSNP: rs12946
Type: single nucleotide variant
Location: chr19:50858059 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.78 · 6 PDB
Residue 79: 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-ser79 (accessed [today's date]).

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