Is SOX5 p.Pro320fs (c.959del) pathogenic?

SOX5 p.Pro320fs (c.959del) is classified Pathogenic in SOX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-10). No gnomAD frequency available for this variant; Associated with Lamb-Shaffer syndrome.

What condition is associated with SOX5 p.Pro320fs (c.959del)?

SOX5 p.Pro320fs (c.959del) is associated with Lamb-Shaffer syndrome (ClinVar).

How common is SOX5 p.Pro320fs (c.959del) in the general population?

SOX5 p.Pro320fs (c.959del) is no gnomAD frequency available for this variant (gnomAD).

How is Lamb-Shaffer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

SOX5 p.Pro320fs

c.959del · rs2079966010 · VCV979189

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

Lamb-Shaffer 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 8 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.058	GERP -1.7, 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: SOX5
Protein: p.Pro320fs
Coding: c.959del
MANE Select: NM_006940
dbSNP: rs2079966010
Type: Deletion
Location: chr12:23640870 (GRCh38)
Gene constraint: LOEUF 0.204 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.95

Full SOX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Lamb-Shaffer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

SOX5 c.1489-7709_1771+1399del Likely pathogenic ★ same condition
SOX5 c.1489del Pathogenic ★ same condition
SOX5 p.Ala241fs Likely pathogenic ★ same condition
SOX5 p.Arg250fs Pathogenic ★ same condition
SOX5 p.Gln75fs Likely pathogenic ★ same condition
SOX5 p.Ile319fs Likely pathogenic ★ same condition
SOX5 p.Phe185fs Pathogenic ★ same condition
SOX5 p.Pro621fs 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/sox5-p-pro320fs (accessed [today's date]).

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