Is SIN3A p.His31Arg (c.92A>G) pathogenic?

SIN3A p.His31Arg (c.92A>G) is classified Uncertain significance in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-19). AlphaMissense: ambiguous (0.3424); Absent from gnomAD v4.1; Associated with SIN3A-related intellectual disability syndrome due to a point mutation.

What condition is associated with SIN3A p.His31Arg (c.92A>G)?

SIN3A p.His31Arg (c.92A>G) is associated with SIN3A-related intellectual disability syndrome due to a point mutation (ClinVar).

How common is SIN3A p.His31Arg (c.92A>G) in the general population?

SIN3A p.His31Arg (c.92A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SIN3A p.His31Arg (c.92A>G)?

AlphaMissense predicts ambiguous (score 0.3424) — an in-silico prediction, not a clinical call.

SIN3A p.His31Arg

c.92A>G · rs2542788602 · VCV3255058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3424 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

SIN3A-related intellectual disability syndrome due to a point mutation

Computational evidence

Protein change
AlphaMissense	0.3424	ambiguous
REVEL	0.138	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 17 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	23.7	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.His31Arg
Coding: c.92A>G
MANE Select: NM_001145358
dbSNP: rs2542788602
Type: single nucleotide variant
Location: chr15:75430284 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67

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.His31= 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
SIN3A p.Arg1205His Uncertain significance ★★ same condition
SIN3A p.Gly733Arg Uncertain significance ★★ ⚠ same condition
SIN3A p.Gly829Arg 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-his31arg (accessed [today's date]).

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