Is KL p.Ala5= (c.15C>T) pathogenic?

KL p.Ala5= (c.15C>T) is classified Conflicting classifications of pathogenicity in KL (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-16). Rare (popmax 0.175%, nfe); Associated with tumoral calcinosis, hyperphosphatemic, familial, 3.

What condition is associated with KL p.Ala5= (c.15C>T)?

KL p.Ala5= (c.15C>T) is associated with tumoral calcinosis, hyperphosphatemic, familial, 3 (ClinVar).

How common is KL p.Ala5= (c.15C>T) in the general population?

KL p.Ala5= (c.15C>T) is rare (popmax 0.175%, nfe) (gnomAD).

How is Familial tumoral calcinosis inherited?

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

KL p.Ala5=

c.15C>T · rs934153273 · VCV881364

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.175%, 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 2	GERP 0.88, phastCons 0.91
Overall
CADD	12.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.175% European (non-Finnish) · 1,418/812,500 alleles

Filtering AF 0.167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.151% 1,459/964,242 alleles · rare exomes 1,328/820,536 · genomes 131/143,706 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.175%	573
Remaining individualsnot grpmax-eligible	0.0892%	1,121
African / African-American	0.025%	4,006
Ashkenazi Jewishnot grpmax-eligible	0.0117%	8,550

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.Ala5=
Coding: c.15C>T
MANE Select: NM_004795
dbSNP: rs934153273
Type: single nucleotide variant
Location: chr13:33016455 (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

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-ala5 (accessed [today's date]).

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