Is SIN3A p.Val504fs (c.1509dup) pathogenic?

SIN3A p.Val504fs (c.1509dup) is classified Pathogenic in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). Absent from gnomAD.

How common is SIN3A p.Val504fs (c.1509dup) in the general population?

SIN3A p.Val504fs (c.1509dup) is absent from gnomAD (gnomAD).

SIN3A p.Val504fs

c.1509dup · rs2542638910 · VCV2702272

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SIN3A
Protein: p.Val504fs
Coding: c.1509dup
MANE Select: NM_001145358
dbSNP: rs2542638910
Type: Duplication
Location: chr15:75401868 (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

Similar variants

SIN3A p.Val504Asp Likely pathogenic ★ same residue
SIN3A p.Asp323fs Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Tyr1105Ter Pathogenic ★★ same type
SIN3A c.474-6dup Benign/Likely benign ★★ same type
SIN3A c.3384dup Pathogenic ★ same type
SIN3A c.474-574_1408-735dup Pathogenic ★ same type
SIN3A p.Ala847fs Pathogenic ★ same type
SIN3A p.Arg984fs Likely pathogenic ★ 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/sin3a-p-val504fs (accessed [today's date]).

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