Is SIN3A p.Arg642Cys (c.1924C>T) pathogenic?

SIN3A p.Arg642Cys (c.1924C>T) is classified Uncertain significance in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-07). AlphaMissense: ambiguous (0.5256); Very rare (popmax 0.000339%, nfe).

How common is SIN3A p.Arg642Cys (c.1924C>T) in the general population?

SIN3A p.Arg642Cys (c.1924C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about SIN3A p.Arg642Cys (c.1924C>T)?

AlphaMissense predicts ambiguous (score 0.5256) — an in-silico prediction, not a clinical call.

SIN3A p.Arg642Cys

c.1924C>T · rs1064796962 · VCV424426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5256	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -10.77	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 11 kb · p 3.7e-14 · regional, not allelic
Overall
CADD	33.0	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 0.000339% European (non-Finnish) · 4/1,179,968 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,804 alleles · very rare

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.Arg642Cys
Coding: c.1924C>T
MANE Select: NM_001145358
dbSNP: rs1064796962
Type: single nucleotide variant
Location: chr15:75396427 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 642: the 'interaction with ncor1' region; the 'interaction with suds3 and sap130' region

Full SIN3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SIN3A p.Arg1140Ter Pathogenic ★★ same type
SIN3A p.Arg471Ter Pathogenic ★★ same type
SIN3A p.Arg537Ter Pathogenic ★★ same type
SIN3A p.Arg553Ter Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Arg559Ter Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Arg718Ter Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Arg897Ter Pathogenic ★★ same type
SIN3A p.Arg935Ter Pathogenic/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-arg642cys (accessed [today's date]).

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