Is SIN3A p.Arg32Gln (c.95G>A) pathogenic?

SIN3A p.Arg32Gln (c.95G>A) is classified Uncertain significance in SIN3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-22). AlphaMissense: ambiguous (0.3775); Very rare (popmax 0.0011%, nfe); Associated with SIN3A-related disorder.

What condition is associated with SIN3A p.Arg32Gln (c.95G>A)?

SIN3A p.Arg32Gln (c.95G>A) is associated with SIN3A-related disorder (ClinVar).

How common is SIN3A p.Arg32Gln (c.95G>A) in the general population?

SIN3A p.Arg32Gln (c.95G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about SIN3A p.Arg32Gln (c.95G>A)?

AlphaMissense predicts ambiguous (score 0.3775) — an in-silico prediction, not a clinical call.

SIN3A p.Arg32Gln

c.95G>A · rs772942517 · VCV3030882

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

SIN3A-related disorder

Computational evidence

Protein change
AlphaMissense	0.3775	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -5.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 17 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,024 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,613,992 alleles · very rare

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.Arg32Gln
Coding: c.95G>A
MANE Select: NM_001145358
dbSNP: rs772942517
Type: single nucleotide variant
Location: chr15:75430281 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67

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

Disease context

SIN3A-related disorder

Similar variants

SIN3A p.Arg559Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Asp975Asn Uncertain significance ★★ ⚠ same condition
SIN3A p.Gln900Ter Pathogenic ★ same condition
SIN3A p.Tyr1174Ter Likely pathogenic ★ same condition
SIN3A p.Asp939Glu Uncertain significance ★ ⚠ same condition
SIN3A p.Ser274Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
SIN3A p.Val200Ala Uncertain significance ★ ⚠ same condition
SIN3A p.Arg1134= 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/sin3a-p-arg32gln (accessed [today's date]).

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