Is SIN3B p.Pro94Arg (c.281C>G) pathogenic?

SIN3B p.Pro94Arg (c.281C>G) is classified Uncertain significance in SIN3B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: ambiguous (0.5248); Absent from gnomAD v4.1.

How common is SIN3B p.Pro94Arg (c.281C>G) in the general population?

SIN3B p.Pro94Arg (c.281C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SIN3B p.Pro94Arg (c.281C>G)?

AlphaMissense predicts ambiguous (score 0.5248) — an in-silico prediction, not a clinical call.

SIN3B p.Pro94Arg

c.281C>G · rs2513024440 · VCV2290497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5248 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5248	ambiguous
REVEL	0.409	indeterminate
SaProt	LLR -9.85	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 33 kb · p 7e-09 · regional, not allelic
Overall
CADD	27.8	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

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.Pro94Arg
Coding: c.281C>G
MANE Select: NM_001297595
dbSNP: rs2513024440
Type: single nucleotide variant
Location: chr19:16831547 (GRCh38)
Gene constraint: LOEUF 0.245 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.07 · 4 PDB
Residue 94: 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

Similar variants

SIN3B p.Ala534Thr Uncertain significance ★★ same type
SIN3B p.Glu258Asp Uncertain significance ★★ ⚠ same type
SIN3B p.His91Tyr Uncertain significance ★★ ⚠ same type
SIN3B p.Pro281Ala Uncertain significance ★★ ⚠ same type
SIN3B p.Val160Met Uncertain significance ★★ ⚠ same type
SIN3B p.Val873Ile Uncertain significance ★★ ⚠ same type
SIN3B c.1266+354G>A Benign ★★ same type
SIN3B c.2954+6A>G Benign ★★ same type

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-pro94arg (accessed [today's date]).

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