Is ALPL p.Asn49= (c.147C>T) pathogenic?

ALPL p.Asn49= (c.147C>T) is classified Likely benign in ALPL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with ALPL p.Asn49= (c.147C>T)?

ALPL p.Asn49= (c.147C>T) is associated with Inborn genetic diseases, infantile hypophosphatasia (ClinVar).

How common is ALPL p.Asn49= (c.147C>T) in the general population?

ALPL p.Asn49= (c.147C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

ALPL p.Asn49=

c.147C>T · rs539884496 · VCV554846

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.288	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.65 · evaluated, not missing
Constraint at this position
Conservation	phyloP -14	GERP -3.5
Overall
CADD	1.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,888 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00217% 35/1,614,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,413
European (non-Finnish)	0.0022%	45,386
South Asian	0.0022%	45,545

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.Asn49=
Coding: c.147C>T
MANE Select: NM_000478
dbSNP: rs539884496
Type: single nucleotide variant
Location: chr1:21560711 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: infantile hypophosphatasia

Similar variants

ALPL p.Asn49Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
ALPL p.Asn49Ile Likely pathogenic ★★ same residue
ALPL p.Asn49Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ALPL c.62-1G>C Pathogenic/Likely pathogenic ★★ same condition
ALPL c.648+1G>A Pathogenic ★★ same condition
ALPL c.649-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALPL c.862+1G>A Pathogenic ★★ same condition
ALPL c.997+1G>T Pathogenic/Likely 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-asn49 (accessed [today's date]).

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