Is KL p.Asp91= (c.273T>C) pathogenic?

KL p.Asp91= (c.273T>C) is classified Benign in KL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with tumoral calcinosis, hyperphosphatemic, familial, 3.

What condition is associated with KL p.Asp91= (c.273T>C)?

KL p.Asp91= (c.273T>C) is associated with tumoral calcinosis, hyperphosphatemic, familial, 3 (ClinVar).

How is Familial tumoral calcinosis inherited?

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

KL p.Asp91=

Q: How common is KL p.Asp91= (c.273T>C) in the general population?

KL p.Asp91= (c.273T>C) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.273T>C · rs2772364 · VCV311680

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

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 2.9	GERP -1.6, phastCons 1
Overall
CADD	13.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,694/44,694 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99% 1,594,934/1,610,264 alleles · common exomes 1,450,643/1,458,290 · genomes 144,291/151,974 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Finnishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
European (non-Finnish)	100%	1
Ashkenazi Jewishnot grpmax-eligible	99.9%	1
South Asian	99.9%	1
Middle Eastern	99%	1
Remaining individualsnot grpmax-eligible	98.7%	1
Admixed American	98.7%	1
African / African-American	82.4%	1

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.Asp91=
Coding: c.273T>C
MANE Select: NM_004795
dbSNP: rs2772364
Type: single nucleotide variant
Location: chr13:33016713 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 6 PDB
Residue 91: an α-helix; 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-asp91 (accessed [today's date]).

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