Is KL p.Ala162= (c.486G>A) pathogenic?

KL p.Ala162= (c.486G>A) is classified Benign/Likely benign in KL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). Rare (popmax 0.699%, sas); Associated with tumoral calcinosis, hyperphosphatemic, familial, 3.

What condition is associated with KL p.Ala162= (c.486G>A)?

KL p.Ala162= (c.486G>A) is associated with tumoral calcinosis, hyperphosphatemic, familial, 3 (ClinVar).

How common is KL p.Ala162= (c.486G>A) in the general population?

KL p.Ala162= (c.486G>A) is rare (popmax 0.699%, sas) (gnomAD).

How is Familial tumoral calcinosis inherited?

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

KL p.Ala162=

c.486G>A · rs371131557 · VCV1537092

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.699%, sas)

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 1.1	GERP -1.6, phastCons 1
Overall
CADD	12.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.699% South Asian · 635/90,824 alleles

Filtering AF 0.654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.636%

Overall 0.0421% 678/1,610,324 alleles · rare exomes 622/1,457,988 · genomes 56/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.699%	143
Remaining individualsnot grpmax-eligible	0.0449%	2,226
Middle Eastern	0.0166%	6,032
Admixed American	0.00501%	19,968
African / African-American	0.00133%	75,032
European (non-Finnish)	0.000848%	117,925

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.Ala162=
Coding: c.486G>A
MANE Select: NM_004795
dbSNP: rs371131557
Type: single nucleotide variant
Location: chr13:33016926 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 6 PDB
Residue 162: 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 p.Ala162Val Uncertain significance ★ ⚠ same residue
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

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-ala162 (accessed [today's date]).

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