Is SIN3A p.Asn751Ser (c.2252A>G) pathogenic?

SIN3A p.Asn751Ser (c.2252A>G) is classified Conflicting classifications of pathogenicity in SIN3A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.0812); Ultra-rare (popmax 0.0669%, eas); Associated with Inborn genetic diseases.

What condition is associated with SIN3A p.Asn751Ser (c.2252A>G)?

SIN3A p.Asn751Ser (c.2252A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SIN3A p.Asn751Ser (c.2252A>G) in the general population?

SIN3A p.Asn751Ser (c.2252A>G) is ultra-rare (popmax 0.0669%, eas) (gnomAD).

What do computational predictors say about SIN3A p.Asn751Ser (c.2252A>G)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

SIN3A p.Asn751Ser

c.2252A>G · rs532044975 · VCV2075705

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -8.58	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 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 23 kb · p 1.4e-14 · regional, not allelic
Overall
CADD	24.6	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 0.0669% East Asian · 30/44,854 alleles

Filtering AF 0.0481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.00663% 107/1,613,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0669%	1,495
Middle Eastern	0.033%	3,030
Admixed American	0.02%	4,993
African / African-American	0.00533%	18,753
European (non-Finnish)	0.00449%	22,261
South Asian	0.0044%	22,747
Remaining individualsnot grpmax-eligible	0.0032%	31,246

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.Asn751Ser
Coding: c.2252A>G
MANE Select: NM_001145358
dbSNP: rs532044975
Type: single nucleotide variant
Location: chr15:75394705 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 751: the 'interaction with ncor1' region; the 'interaction with hdac1 and arid4b' 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.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
SIN3A p.Gly72Ser 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-asn751ser (accessed [today's date]).

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