Is KL p.Ser150= (c.450C>A) pathogenic?

KL p.Ser150= (c.450C>A) is classified Conflicting classifications of pathogenicity in KL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-06). Very rare (popmax 0.00331%, nfe); Associated with tumoral calcinosis, hyperphosphatemic, familial, 3.

What condition is associated with KL p.Ser150= (c.450C>A)?

KL p.Ser150= (c.450C>A) is associated with tumoral calcinosis, hyperphosphatemic, familial, 3 (ClinVar).

How common is KL p.Ser150= (c.450C>A) in the general population?

KL p.Ser150= (c.450C>A) is very rare (popmax 0.00331%, nfe) (gnomAD).

How is Familial tumoral calcinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

KL p.Ser150=

c.450C>A · rs764992732 · VCV882962

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Conditions

tumoral calcinosis, hyperphosphatemic, familial, 3

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 0.52	GERP -3.8, phastCons 1
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00331% European (non-Finnish) · 39/1,179,786 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00763% 123/1,612,386 alleles · very rare exomes 107/1,460,226 · genomes 16/152,160 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.247%	405
Remaining individualsnot grpmax-eligible	0.016%	6,241
European (non-Finnish)grpmax	0.00331%	30,251
Admixed American	0.00167%	59,982

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser150=
Coding: c.450C>A
MANE Select: NM_004795
dbSNP: rs764992732
Type: single nucleotide variant
Location: chr13:33016890 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 6 PDB
Residue 150: a β-strand; the 'glycosyl hydrolase-1 1' region

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

Disease context

tumoral calcinosis, hyperphosphatemic, familial, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial tumoral calcinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

KL c.1331-3C>A Uncertain significance ★★ same condition
KL p.Ala987Thr Uncertain significance ★★ ⚠ same condition
KL p.Arg179Trp Uncertain significance ★★ ⚠ same condition
KL p.Arg594Cys Uncertain significance ★★ ⚠ same condition
KL p.Arg620Cys Uncertain significance ★★ ⚠ same condition
KL p.Arg628Cys Uncertain significance ★★ ⚠ same condition
KL p.Arg751Gly Uncertain significance ★★ ⚠ same condition
KL p.Arg853Cys 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/kl-p-ser150 (accessed [today's date]).

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