Is SIN3B p.Ser677= (c.2031C>T) pathogenic?

SIN3B p.Ser677= (c.2031C>T) is classified Likely benign in SIN3B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Ultra-rare (popmax 0.0445%, eas); Associated with SIN3B-related disorder.

What condition is associated with SIN3B p.Ser677= (c.2031C>T)?

SIN3B p.Ser677= (c.2031C>T) is associated with SIN3B-related disorder (ClinVar).

How common is SIN3B p.Ser677= (c.2031C>T) in the general population?

SIN3B p.Ser677= (c.2031C>T) is ultra-rare (popmax 0.0445%, eas) (gnomAD).

SIN3B p.Ser677=

c.2031C>T · rs763134125 · VCV3042916

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, eas)

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 -20	GERP -4.6
Overall
CADD	0.051	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0445% East Asian · 20/44,902 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00378% 61/1,613,416 alleles · ultra-rare exomes 54/1,461,194 · genomes 7/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0445%	2,245
African / African-American	0.028%	3,568
Middle Eastern	0.0164%	6,080
South Asian	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0064%	15,619
Admixed American	0.00167%	60,012
European (non-Finnish)	0.000593%	168,575

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.Ser677=
Coding: c.2031C>T
MANE Select: NM_001297595
dbSNP: rs763134125
Type: single nucleotide variant
Location: chr19:16869684 (GRCh38)
Gene constraint: LOEUF 0.245 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.07 · 4 PDB
Residue 677: a β-strand

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-ser677 (accessed [today's date]).

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