Is SIN3A p.Ala455fs (c.1363del) pathogenic?

SIN3A p.Ala455fs (c.1363del) is classified Pathogenic in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-29). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with SIN3A p.Ala455fs (c.1363del)?

SIN3A p.Ala455fs (c.1363del) is associated with Inborn genetic diseases (ClinVar).

How common is SIN3A p.Ala455fs (c.1363del) in the general population?

SIN3A p.Ala455fs (c.1363del) is absent from gnomAD (gnomAD).

SIN3A p.Ala455fs

c.1363del · rs2542665267 · VCV2616550

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

Conditions

Inborn genetic diseases

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 9 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 0.58, 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.Ala455fs
Coding: c.1363del
MANE Select: NM_001145358
dbSNP: rs2542665267
Type: Deletion
Location: chr15:75407099 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 455: the 'interaction with rest' 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.Gln827fs Pathogenic ★ same condition
SIN3A p.Glu526fs Pathogenic ★ same condition
SIN3A p.Val81fs Pathogenic ★ same condition
SIN3A c.1854+30_1854+32del Uncertain significance ★ same condition
SIN3A p.Arg553Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Tyr1105Ter Pathogenic ★★ same condition
SIN3A p.Ala242Thr Uncertain significance ★★ ⚠ same condition
SIN3A p.Arg19Trp 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-ala455fs (accessed [today's date]).

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