Is SIN3A p.Ser476= (c.1428T>C) pathogenic?

SIN3A p.Ser476= (c.1428T>C) is classified Benign/Likely benign in SIN3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-31). Low-frequency (popmax 2.15%, afr); Associated with SIN3A-related intellectual disability syndrome due to a point mutation.

What condition is associated with SIN3A p.Ser476= (c.1428T>C)?

SIN3A p.Ser476= (c.1428T>C) is associated with SIN3A-related intellectual disability syndrome due to a point mutation (ClinVar).

How common is SIN3A p.Ser476= (c.1428T>C) in the general population?

SIN3A p.Ser476= (c.1428T>C) is low-frequency (popmax 2.15%, afr) (gnomAD).

SIN3A p.Ser476=

c.1428T>C · rs58376508 · VCV779901

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.15%, afr)

Conditions

SIN3A-related intellectual disability syndrome due to a point mutation

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 0.59	GERP -3.6, phastCons 0.72
Overall
CADD	7.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.15% African / African-American · 1,613/74,992 alleles

Filtering AF 2.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.03%

Overall 0.122% 1,967/1,612,618 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.15%	46
Remaining individualsnot grpmax-eligible	0.191%	525
Admixed American	0.182%	550
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.00976%	10,250
South Asian	0.00549%	18,209

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: SIN3A
Protein: p.Ser476=
Coding: c.1428T>C
MANE Select: NM_001145358
dbSNP: rs58376508
Type: single nucleotide variant
Location: chr15:75401950 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 476: the 'interaction with sap30' region; the pah 3 domain; the 'interaction with rest' region

Full SIN3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SIN3A-related intellectual disability syndrome due to a point mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SIN3A p.Arg1140Ter Pathogenic ★★ same condition
SIN3A p.Arg471Ter Pathogenic ★★ same condition
SIN3A p.Arg718Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Arg935Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Arg1205His Uncertain significance ★★ same condition
SIN3A p.Gly733Arg Uncertain significance ★★ ⚠ same condition
SIN3A p.Gly829Arg Uncertain significance ★★ ⚠ same condition
SIN3A p.Gly96Ser Uncertain significance ★★ ⚠ 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/sin3a-p-ser476 (accessed [today's date]).

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