Is SON p.Arg2008Ter (c.6022C>T) pathogenic?

SON p.Arg2008Ter (c.6022C>T) is classified Pathogenic in SON (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-10-30). Absent from gnomAD v4.1; Associated with ZTTK syndrome.

What condition is associated with SON p.Arg2008Ter (c.6022C>T)?

SON p.Arg2008Ter (c.6022C>T) is associated with ZTTK syndrome (ClinVar).

How common is SON p.Arg2008Ter (c.6022C>T) in the general population?

SON p.Arg2008Ter (c.6022C>T) is absent from gnomAD v4.1 (gnomAD).

SON p.Arg2008Ter

c.6022C>T · rs1555899560 · VCV453018

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ZTTK syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 3.5, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SON
Protein: p.Arg2008Ter
Coding: c.6022C>T
MANE Select: NM_138927
dbSNP: rs1555899560
Type: single nucleotide variant
Location: chr21:33555253 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 2008: the 'disordered' region; the '2 x 19 aa repeats of p-s-r-r-r-r-s-r-s-v-v-r-r-r-s-f-s-i-s' 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 c.6321+1G>A Pathogenic ★★ same condition
SON p.Arg1081Ter Pathogenic ★★ same condition
SON p.Arg1112Ter Pathogenic ★★ same condition
SON p.Gln96Ter Pathogenic/Likely pathogenic ★★ same condition
SON c.6657+316G>A Uncertain significance ★★ same condition
SON p.Ala817Ser Uncertain significance ★★ ⚠ same condition
SON p.Ala847Pro Uncertain significance ★★ ⚠ same condition
SON p.Arg1039His Uncertain significance ★★ ⚠ 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-arg2008ter (accessed [today's date]).

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