Is SIN3A p.Pro270Ala (c.808C>G) pathogenic?

SIN3A p.Pro270Ala (c.808C>G) is classified Likely benign in SIN3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.0618); Ultra-rare (popmax 0.0684%, amr); Associated with Inborn genetic diseases.

What condition is associated with SIN3A p.Pro270Ala (c.808C>G)?

SIN3A p.Pro270Ala (c.808C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SIN3A p.Pro270Ala (c.808C>G) in the general population?

SIN3A p.Pro270Ala (c.808C>G) is ultra-rare (popmax 0.0684%, amr) (gnomAD).

What do computational predictors say about SIN3A p.Pro270Ala (c.808C>G)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

SIN3A p.Pro270Ala

c.808C>G · rs749431910 · VCV2039533

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 1,340 bp · p 0.042 · regional, not allelic
Overall
CADD	24.5	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 0.0684% Admixed American · 41/59,964 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.0026% 42/1,613,180 alleles · ultra-rare exomes 39/1,460,954 · genomes 3/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0684%	1,463
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Pro270Ala
Coding: c.808C>G
MANE Select: NM_001145358
dbSNP: rs749431910
Type: single nucleotide variant
Location: chr15:75411692 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 270: the 'interaction with rest' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SIN3A p.Pro270= Likely benign ★ same residue
SIN3A p.Arg553Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Ala242Thr Uncertain significance ★★ ⚠ same condition
SIN3A p.Arg19Trp Uncertain significance ★★ ⚠ same condition
SIN3A p.Arg471Gln Uncertain significance ★★ ⚠ same condition
SIN3A p.Asn1151Lys Uncertain significance ★★ ⚠ same condition
SIN3A p.Asn414Thr Uncertain significance ★★ ⚠ same condition
SIN3A p.Gln1208His 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-pro270ala (accessed [today's date]).

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