Is SON p.Asp1819fs (c.5455_5456dup) pathogenic?

SON p.Asp1819fs (c.54555456dup) is classified Likely pathogenic in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). No gnomAD frequency available for this variant; Associated with ZTTK syndrome.

What condition is associated with SON p.Asp1819fs (c.5455_5456dup)?

SON p.Asp1819fs (c.5455_5456dup) is associated with ZTTK syndrome (ClinVar).

How common is SON p.Asp1819fs (c.5455_5456dup) in the general population?

SON p.Asp1819fs (c.5455_5456dup) is no gnomAD frequency available for this variant (gnomAD).

SON p.Asp1819fs

c.5455_5456dup · rs2517391196 · VCV1803075

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ZTTK syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 4.2, 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: SON
Protein: p.Asp1819fs
Coding: c.5455_5456dup
MANE Select: NM_138927
dbSNP: rs2517391196
Type: Microsatellite
Location: chr21:33554682 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 1819: the 'disordered' region

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

Disease context

ZTTK syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SON p.Gln874fs Pathogenic ★★ same condition
SON p.Arg1850fs Pathogenic ★ same condition
SON p.Glu1206fs Pathogenic ★ same condition
SON p.Arg1884del Uncertain significance ★ same condition
SON p.Thr694del Uncertain significance ★ same condition
SON p.Asp1819= Likely benign ★ same residue
SON p.Thr1453fs Likely pathogenic same condition
SON c.6321+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/son-p-asp1819fs (accessed [today's date]).

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