Is SIN3A p.Val504Asp (c.1511T>A) pathogenic?

SIN3A p.Val504Asp (c.1511T>A) is classified Likely pathogenic in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely pathogenic (0.9956); Absent from gnomAD v4.1; Associated with SIN3A-related intellectual disability syndrome due to a point mutation.

What condition is associated with SIN3A p.Val504Asp (c.1511T>A)?

SIN3A p.Val504Asp (c.1511T>A) is associated with SIN3A-related intellectual disability syndrome due to a point mutation (ClinVar).

How common is SIN3A p.Val504Asp (c.1511T>A) in the general population?

SIN3A p.Val504Asp (c.1511T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SIN3A p.Val504Asp (c.1511T>A)?

AlphaMissense predicts likely pathogenic (score 0.9956) — an in-silico prediction, not a clinical call.

SIN3A p.Val504Asp

c.1511T>A · VCV3258084

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SIN3A-related intellectual disability syndrome due to a point mutation

Computational evidence

Protein change
AlphaMissense	0.9956	likely pathogenic ✓ concordant with ClinVar
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -15.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 11 kb · p 3.7e-14 · regional, not allelic
Overall
CADD	29.8	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: SIN3A
Protein: p.Val504Asp
Coding: c.1511T>A
MANE Select: NM_001145358
Type: single nucleotide variant
Location: chr15:75401867 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 504: the 'interaction with sap30' region; the pah 3 domain

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

Disease context

SIN3A-related intellectual disability syndrome due to a point mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SIN3A p.Arg1140Ter Pathogenic ★★ same condition
SIN3A p.Arg471Ter Pathogenic ★★ same condition
SIN3A p.Arg718Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Arg935Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Arg1205His Uncertain significance ★★ same condition
SIN3A p.Gly733Arg Uncertain significance ★★ ⚠ same condition
SIN3A p.Gly829Arg Uncertain significance ★★ ⚠ same condition
SIN3A p.Gly96Ser 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-val504asp (accessed [today's date]).

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