Is SIN3B p.Thr192= (c.576G>A) pathogenic?

SIN3B p.Thr192= (c.576G>A) is classified Likely benign in SIN3B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-30). Ultra-rare (popmax 0.0165%, mid); Associated with SIN3B-related disorder.

What condition is associated with SIN3B p.Thr192= (c.576G>A)?

SIN3B p.Thr192= (c.576G>A) is associated with SIN3B-related disorder (ClinVar).

How common is SIN3B p.Thr192= (c.576G>A) in the general population?

SIN3B p.Thr192= (c.576G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

SIN3B p.Thr192=

c.576G>A · rs373254965 · VCV3034782

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

SIN3B-related disorder

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 -4.2	GERP -4.6
Overall
CADD	3.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00062% 10/1,612,984 alleles · ultra-rare exomes 10/1,460,750 · genomes 0/152,234 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00333%	30,007
European (non-Finnish)	0.000594%	168,449

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: SIN3B
Protein: p.Thr192=
Coding: c.576G>A
MANE Select: NM_001297595
dbSNP: rs373254965
Type: single nucleotide variant
Location: chr19:16841962 (GRCh38)
Gene constraint: LOEUF 0.245 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.07 · 4 PDB
Residue 192: the pah 2 domain; the 'interaction with cry1' region

Full SIN3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SIN3B-related disorder

Similar variants

SIN3B p.Gln984Ter Likely pathogenic ★ same condition
SIN3B c.1384-2A>G Uncertain significance ★ same condition
SIN3B c.1623-5C>A Uncertain significance ★ same condition
SIN3B p.Gln75= Uncertain significance ★ same condition
SIN3B p.Glu780Asp Uncertain significance ★ ⚠ same condition
SIN3B p.Thr244Arg Uncertain significance ★ ⚠ same condition
SIN3B c.2423-4G>A Likely benign same condition
SIN3B c.2955-7C>T Likely benign 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/sin3b-p-thr192 (accessed [today's date]).

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