Is KL p.Pro12= (c.36G>A) pathogenic?

KL p.Pro12= (c.36G>A) is classified Likely benign in KL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). Very rare (popmax 0.0084%, afr).

How common is KL p.Pro12= (c.36G>A) in the general population?

KL p.Pro12= (c.36G>A) is very rare (popmax 0.0084%, afr) (gnomAD).

KL p.Pro12=

c.36G>A · rs911447021 · VCV2785144

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0084%, 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 -0.26	GERP -1.2
Overall
CADD	6.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0084% African / African-American · 5/59,518 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.000549% 6/1,093,280 alleles · very rare exomes 2/946,754 · genomes 4/146,526 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0084%	11,904
European (non-Finnish)	0.000111%	900,836

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: KL
Protein: p.Pro12=
Coding: c.36G>A
MANE Select: NM_004795
dbSNP: rs911447021
Type: single nucleotide variant
Location: chr13:33016476 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 6 PDB

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

Similar variants

KL c.1331-3C>A Uncertain significance ★★ same type
KL p.Ala3Thr Uncertain significance ★★ ⚠ same type
KL p.Ala50Val Uncertain significance ★★ ⚠ same type
KL p.Ala656Thr Uncertain significance ★★ ⚠ same type
KL p.Ala663Thr Uncertain significance ★★ ⚠ same type
KL p.Ala987Thr Uncertain significance ★★ ⚠ same type
KL p.Arg179Trp Uncertain significance ★★ ⚠ same type
KL p.Arg181Gln 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/kl-p-pro12 (accessed [today's date]).

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