Is SIN3B p.Gln75= (c.225G>A) pathogenic?

SIN3B p.Gln75= (c.225G>A) is classified Uncertain significance in SIN3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-25). Absent from gnomAD v4.1; Associated with SIN3B-related disorder.

What condition is associated with SIN3B p.Gln75= (c.225G>A)?

SIN3B p.Gln75= (c.225G>A) is associated with SIN3B-related disorder (ClinVar).

How common is SIN3B p.Gln75= (c.225G>A) in the general population?

SIN3B p.Gln75= (c.225G>A) is absent from gnomAD v4.1 (gnomAD).

SIN3B p.Gln75=

c.225G>A · VCV4855530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

SIN3B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.89, phastCons 1
Overall
CADD	14.31	PHRED · no single calibrated threshold — expert panels disagree

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: SIN3B
Protein: p.Gln75=
Coding: c.225G>A
MANE Select: NM_001297595
Type: single nucleotide variant
Location: chr19:16829895 (GRCh38)
Gene constraint: LOEUF 0.245 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.07 · 4 PDB
Residue 75: the pah 1 domain; the 'interaction with cry1' region; the 'interaction with rest' 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.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
SIN3B c.3162+5C>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-gln75 (accessed [today's date]).

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