Is ALPL p.Val434fs (c.1286_1299dup) pathogenic?

ALPL p.Val434fs (c.12861299dup) is classified Pathogenic in ALPL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-19). Absent from gnomAD.

How common is ALPL p.Val434fs (c.1286_1299dup) in the general population?

ALPL p.Val434fs (c.1286_1299dup) is absent from gnomAD (gnomAD).

ALPL p.Val434fs

c.1286_1299dup · rs2148192656 · VCV1457899

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (11 of 12, 25 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.55	GERP -2.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALPL
Protein: p.Val434fs
Coding: c.1286_1299dup
MANE Select: NM_000478
dbSNP: rs2148192656
Type: Duplication
Location: chr1:21576616 (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

Similar variants

ALPL p.Val434= Uncertain significance same residue
ALPL p.Arg391fs Pathogenic/Likely pathogenic ★★ same type
ALPL p.Gln361fs Pathogenic ★★ same type
ALPL p.Gly222fs Pathogenic/Likely pathogenic ★★ same type
ALPL p.His340fs Pathogenic ★★ same type
ALPL p.His482fs Likely pathogenic ★★ same type
ALPL p.Val130fs Pathogenic/Likely pathogenic ★★ same type
ALPL c.183dupG Pathogenic ★ same type

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-val434fs (accessed [today's date]).

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