Is PAPPA2 p.Asp643fs (c.1928_1929insAT) pathogenic?

PAPPA2 p.Asp643fs (c.19281929insAT) is classified Pathogenic in PAPPA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-08-17). No gnomAD frequency available for this variant; Associated with Short stature, Dauber-Argente type.

What condition is associated with PAPPA2 p.Asp643fs (c.1928_1929insAT)?

PAPPA2 p.Asp643fs (c.1928_1929insAT) is associated with Short stature, Dauber-Argente type (ClinVar).

How common is PAPPA2 p.Asp643fs (c.1928_1929insAT) in the general population?

PAPPA2 p.Asp643fs (c.1928_1929insAT) is no gnomAD frequency available for this variant (gnomAD).

PAPPA2 p.Asp643fs

c.1928_1929insAT · rs2102651720 · VCV1202641

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Short stature, Dauber-Argente type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

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: PAPPA2
Protein: p.Asp643fs
Coding: c.1928_1929insAT
MANE Select: NM_020318
dbSNP: rs2102651720
Type: Insertion
Location: chr1:176595532 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.65 · 1 PDB
Residue 643: the 'metalloprotease' region

Full PAPPA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Short stature, Dauber-Argente type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PAPPA2 p.Leu987fs Likely pathogenic ★ same condition
PAPPA2 c.2431+46del Uncertain significance ★ same condition
PAPPA2 c.3798+10C>A Uncertain significance ★ same condition
PAPPA2 p.Ala1033Val Pathogenic same condition
PAPPA2 p.Glu886Ter 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/pappa2-p-asp643fs (accessed [today's date]).

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