Is SIN3A p.Arg19Trp (c.55C>T) pathogenic?

SIN3A p.Arg19Trp (c.55C>T) is classified Uncertain significance in SIN3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). AlphaMissense: ambiguous (0.5064); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SIN3A p.Arg19Trp (c.55C>T)?

SIN3A p.Arg19Trp (c.55C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SIN3A p.Arg19Trp (c.55C>T) in the general population?

SIN3A p.Arg19Trp (c.55C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SIN3A p.Arg19Trp (c.55C>T)?

AlphaMissense predicts ambiguous (score 0.5064) — an in-silico prediction, not a clinical call.

SIN3A p.Arg19Trp

c.55C>T · rs979275524 · VCV2869572

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5064	ambiguous
REVEL	0.244	benign-leaning
SaProt	LLR -10.38	damaging
⇒ SaProt calls this damaging; REVEL does not; 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 0.52, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 17 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.2e-05% 1/1,614,130 alleles · very rare exomes 1/1,461,848 · genomes 0/152,282 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SIN3A
Protein: p.Arg19Trp
Coding: c.55C>T
MANE Select: NM_001145358
dbSNP: rs979275524
Type: single nucleotide variant
Location: chr15:75430321 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 19: the 'disordered' 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.Arg19Gln Uncertain significance ★ ⚠ same residue
SIN3A p.Arg553Ter Pathogenic/Likely pathogenic ★★ same condition
SIN3A p.Ala242Thr Uncertain significance ★★ ⚠ same condition
SIN3A p.Arg471Gln Uncertain significance ★★ ⚠ same condition
SIN3A p.Asn1151Lys Uncertain significance ★★ ⚠ same condition
SIN3A p.Asn414Thr Uncertain significance ★★ ⚠ same condition
SIN3A p.Gln1208His Uncertain significance ★★ ⚠ same condition
SIN3A p.Gly72Ser 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-arg19trp (accessed [today's date]).

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