Is SOX5 p.Pro192= (c.576C>T) pathogenic?

SOX5 p.Pro192= (c.576C>T) is classified Conflicting classifications of pathogenicity in SOX5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-24). Very rare (popmax 0.00452%, eas); Associated with Lamb-Shaffer syndrome.

What condition is associated with SOX5 p.Pro192= (c.576C>T)?

SOX5 p.Pro192= (c.576C>T) is associated with Lamb-Shaffer syndrome (ClinVar).

How common is SOX5 p.Pro192= (c.576C>T) in the general population?

SOX5 p.Pro192= (c.576C>T) is very rare (popmax 0.00452%, eas) (gnomAD).

How is Lamb-Shaffer syndrome inherited?

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

SOX5 p.Pro192=

c.576C>T · rs748012592 · VCV2436259

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00452%, eas)

Conditions

Lamb-Shaffer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -4.3
Overall
CADD	0.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00452% East Asian · 2/44,284 alleles

Filtering AF 0.000894% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000448%

Overall 0.00113% 18/1,592,308 alleles · very rare exomes 15/1,440,272 · genomes 3/152,036 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00452%	22,142
South Asian	0.00337%	29,714
Remaining individualsnot grpmax-eligible	0.00326%	30,694
African / African-American	0.0027%	36,986
Admixed American	0.00174%	57,390
European (non-Finnish)	0.000685%	145,879

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SOX5
Protein: p.Pro192=
Coding: c.576C>T
MANE Select: NM_006940
dbSNP: rs748012592
Type: single nucleotide variant
Location: chr12:23741032 (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.1164+2T>G Pathogenic ★★ same condition
SOX5 p.Arg118Ter Pathogenic ★★ same condition
SOX5 p.Arg213Ter Pathogenic/Likely pathogenic ★★ same condition
SOX5 p.Arg471Ter Pathogenic/Likely pathogenic ★★ same condition
SOX5 p.Arg493Ter Pathogenic ★★ same condition
SOX5 p.Arg558Cys Pathogenic/Likely pathogenic ★★ same condition
SOX5 p.Arg558His Pathogenic/Likely pathogenic ★★ same condition
SOX5 p.Arg571Gln Pathogenic/Likely 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-pro192 (accessed [today's date]).

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