Is SIN3B p.Ser970Arg (c.2910C>G) pathogenic?

SIN3B p.Ser970Arg (c.2910C>G) is classified Uncertain significance in SIN3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.274); Rare (popmax 0.101%, afr).

How common is SIN3B p.Ser970Arg (c.2910C>G) in the general population?

SIN3B p.Ser970Arg (c.2910C>G) is rare (popmax 0.101%, afr) (gnomAD).

What do computational predictors say about SIN3B p.Ser970Arg (c.2910C>G)?

AlphaMissense predicts likely benign (score 0.274) — an in-silico prediction, not a clinical call.

SIN3B p.Ser970Arg

c.2910C>G · rs144154968 · VCV2562079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.274 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.274	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.78	unconstrained · MANE · 7,337 bp · p 8e-06 · regional, not allelic
Overall
CADD	16.19	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S1002R vs ClinVar S970R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% African / African-American · 76/74,926 alleles

Filtering AF 0.083% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.00589% 95/1,612,298 alleles · rare exomes 53/1,460,092 · genomes 42/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	986
Remaining individualsnot grpmax-eligible	0.00801%	12,481
South Asian	0.00442%	22,616
Admixed American	0.00334%	29,901
European (non-Finnish)	0.000678%	147,450

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.Ser970Arg
Coding: c.2910C>G
MANE Select: NM_001297595
dbSNP: rs144154968
Type: single nucleotide variant
Location: chr19:16877595 (GRCh38)
Gene constraint: LOEUF 0.245 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.07 · 4 PDB

Full SIN3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SIN3B p.Ser970Ile Uncertain significance ★ ⚠ same residue
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

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-ser970arg (accessed [today's date]).

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