Is SIN3A p.Ile630Val (c.1888A>G) pathogenic?

SIN3A p.Ile630Val (c.1888A>G) is classified Conflicting classifications of pathogenicity in SIN3A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1279); Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with SIN3A p.Ile630Val (c.1888A>G)?

SIN3A p.Ile630Val (c.1888A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SIN3A p.Ile630Val (c.1888A>G) in the general population?

SIN3A p.Ile630Val (c.1888A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about SIN3A p.Ile630Val (c.1888A>G)?

AlphaMissense predicts likely benign (score 0.1279) — an in-silico prediction, not a clinical call.

SIN3A p.Ile630Val

c.1888A>G · rs201414754 · VCV451316

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1279	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 11 kb · p 3.7e-14 · regional, not allelic
Overall
CADD	24.9	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 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.0018% 29/1,614,034 alleles · very rare exomes 24/1,461,784 · genomes 5/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
Remaining individualsnot grpmax-eligible	0.0064%	15,625
South Asian	0.0022%	45,531
European (non-Finnish)	0.00161%	62,103
African / African-American	0.00133%	75,038

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.Ile630Val
Coding: c.1888A>G
MANE Select: NM_001145358
dbSNP: rs201414754
Type: single nucleotide variant
Location: chr15:75396463 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 630: the 'interaction with ncor1' region; the 'interaction with suds3 and sap130' 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-ile630val (accessed [today's date]).

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