Is ALPL p.Leu287= (c.859T>C) pathogenic?

ALPL p.Leu287= (c.859T>C) is classified Benign/Likely benign in ALPL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.4%, afr); Associated with osteogenesis imperfecta.

What condition is associated with ALPL p.Leu287= (c.859T>C)?

ALPL p.Leu287= (c.859T>C) is associated with osteogenesis imperfecta, hypophosphatasia, adult hypophosphatasia (ClinVar).

How common is ALPL p.Leu287= (c.859T>C) in the general population?

ALPL p.Leu287= (c.859T>C) is rare (popmax 0.4%, afr) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

ALPL p.Leu287=

c.859T>C · rs141742288 · VCV738556

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.4%, afr)

Conditions

osteogenesis imperfecta

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 1.5	GERP 1.6, phastCons 1
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.4% African / African-American · 300/74,978 alleles

Filtering AF 0.363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.348%

Overall 0.0213% 343/1,613,630 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.4%	250
Admixed American	0.0367%	2,727
Remaining individualsnot grpmax-eligible	0.0256%	3,906
South Asian	0.0022%	45,532
European (non-Finnish)	0.000254%	393,238

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: ALPL
Protein: p.Leu287=
Coding: c.859T>C
MANE Select: NM_000478
dbSNP: rs141742288
Type: single nucleotide variant
Location: chr1:21570371 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB
Residue 287: a β-strand

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

Disease context

osteogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypophosphatasia adult hypophosphatasia childhood hypophosphatasia infantile hypophosphatasia

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

ALPL c.1190-2A>T Pathogenic ★★ same condition
ALPL c.182-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALPL c.182-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALPL c.297+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALPL c.298-1G>A Pathogenic ★★ same condition
ALPL c.472+1G>A Pathogenic ★★ same condition
ALPL c.62-1G>C Pathogenic/Likely pathogenic ★★ same condition
ALPL c.648+1G>A Pathogenic ★★ 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/alpl-p-leu287 (accessed [today's date]).

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