Is SIN3A p.Arg167fs (c.499_500insT) pathogenic?

SIN3A p.Arg167fs (c.499500insT) is classified Pathogenic in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Associated with SIN3A-related intellectual disability syndrome due to a point mutation.

What condition is associated with SIN3A p.Arg167fs (c.499_500insT)?

SIN3A p.Arg167fs (c.499_500insT) is associated with SIN3A-related intellectual disability syndrome due to a point mutation (ClinVar).

SIN3A p.Arg167fs

c.499_500insT · VCV4850010

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

SIN3A-related intellectual disability syndrome due to a point mutation

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 5 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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

Variant & gene context

Gene: SIN3A
Protein: p.Arg167fs
Coding: c.499_500insT
MANE Select: NM_001145358
Type: Insertion
Location: chr15:75413019 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 167: the pah 1 domain; the 'interaction with hcfc1' region

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.Val851_Lys852insTer Likely pathogenic ★ same condition
SIN3A p.Arg167His Uncertain significance ★ ⚠ same residue
SIN3A p.Arg167Pro Uncertain significance ★ ⚠ same residue
SIN3A p.Arg167= Likely benign ★ same residue
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

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-arg167fs (accessed [today's date]).

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