Is ALPL p.Thr113= (c.339C>T) pathogenic?

ALPL p.Thr113= (c.339C>T) is classified Likely benign in ALPL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0111%, eas); Associated with childhood hypophosphatasia.

What condition is associated with ALPL p.Thr113= (c.339C>T)?

ALPL p.Thr113= (c.339C>T) is associated with childhood hypophosphatasia, adult hypophosphatasia, infantile hypophosphatasia (ClinVar).

How common is ALPL p.Thr113= (c.339C>T) in the general population?

ALPL p.Thr113= (c.339C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

How is Hypophosphatasia inherited?

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

ALPL p.Thr113=

c.339C>T · rs377453516 · VCV1142227

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

childhood hypophosphatasia

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 -20	GERP -3.9
Overall
CADD	0.192	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,888 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000682% 11/1,613,336 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
African / African-American	0.004%	24,976
Admixed American	0.00167%	60,008
South Asian	0.0011%	91,090
European (non-Finnish)	8.48e-05%	1,179,727

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.Thr113=
Coding: c.339C>T
MANE Select: NM_000478
dbSNP: rs377453516
Type: single nucleotide variant
Location: chr1:21563151 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB
Residue 113: an α-helix

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

Disease context

childhood hypophosphatasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adult hypophosphatasia infantile hypophosphatasia

For Hypophosphatasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

ALPL p.Thr113Ala Uncertain significance ★ ⚠ same residue
ALPL c.1190-2A>T Pathogenic ★★ same condition
ALPL c.298-1G>A Pathogenic ★★ same condition
ALPL c.62-1G>C Pathogenic/Likely pathogenic ★★ same condition
ALPL c.648+1G>A Pathogenic ★★ same condition
ALPL c.648+1G>T Pathogenic ★★ same condition
ALPL c.649-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALPL c.862+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-thr113 (accessed [today's date]).

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