Is SON p.Ser1594fs (c.4779_4780del) pathogenic?

SON p.Ser1594fs (c.47794780del) is classified Pathogenic in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-10). No gnomAD frequency available for this variant; Associated with intellectual disability.

What condition is associated with SON p.Ser1594fs (c.4779_4780del)?

SON p.Ser1594fs (c.4779_4780del) is associated with intellectual disability (ClinVar).

How common is SON p.Ser1594fs (c.4779_4780del) in the general population?

SON p.Ser1594fs (c.4779_4780del) is no gnomAD frequency available for this variant (gnomAD).

SON p.Ser1594fs

c.4779_4780del · rs2085890366 · VCV981435

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

Conditions

intellectual disability

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 0.57	GERP 1.8, phastCons 0.9

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.Ser1594fs
Coding: c.4779_4780del
MANE Select: NM_138927
dbSNP: rs2085890366
Type: Deletion
Location: chr21:33554009 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SON p.Arg1112fs Pathogenic ★ same condition
SON p.Ser1594Cys Uncertain significance ★ ⚠ same residue
SON p.Ser1594Pro Uncertain significance ★ ⚠ same residue
SON p.Met815Leu Benign/Likely benign ★★ ⚠ same condition
SON p.Asn1724Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
SON p.Gln2290Pro Uncertain significance ★ ⚠ same condition
SON p.Pro340Ser Uncertain significance ★ ⚠ same condition
SON p.Tyr1140His 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-ser1594fs (accessed [today's date]).

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