Is KLK7 p.Pro208= (c.624G>T) pathogenic?

KLK7 p.Pro208= (c.624G>T) is classified Benign in KLK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-29). Low-frequency (popmax 1.86%, afr).

How common is KLK7 p.Pro208= (c.624G>T) in the general population?

KLK7 p.Pro208= (c.624G>T) is low-frequency (popmax 1.86%, afr) (gnomAD).

KLK7 p.Pro208=

c.624G>T · rs73932697 · VCV781474

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.86%, afr)

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 -10	GERP -4.6
Overall
CADD	0.412	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.86% African / African-American · 1,394/75,042 alleles

Filtering AF 1.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.74%

Overall 0.0969% 1,564/1,613,300 alleles · low-frequency exomes 753/1,460,984 · genomes 811/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.86%	54
Middle Eastern	0.123%	810
Admixed American	0.115%	870
Remaining individualsnot grpmax-eligible	0.11%	905
European (non-Finnish)	0.00203%	49,165
South Asian	0.0011%	91,048

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: KLK7
Protein: p.Pro208=
Coding: c.624G>T
MANE Select: NM_005046
dbSNP: rs73932697
Type: single nucleotide variant
Location: chr19:50977674 (GRCh38)
Structure: AlphaFold pLDDT 91.72 · 21 PDB
Residue 208: the peptidase s1 domain; a β-strand

Full KLK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KLK7 p.Pro208Leu Uncertain significance ★ ⚠ same residue
KLK7 p.Thr153Met Uncertain significance ★★ ⚠ same type
KLK6 p.Arg78Trp Benign ★★ ⚠ same type
KLK7 p.Cys226= Benign ★★ same type
KLK7 p.Ser147= Benign ★★ same type
KLK7 p.Thr242Ile Benign ★★ same type
KLK6 p.Ala101Thr Uncertain significance ★ ⚠ same type
KLK6 p.Ala101Val Uncertain significance ★ ⚠ same type

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/klk7-p-pro208 (accessed [today's date]).

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