Is SETD1B p.Cys1007= (c.3021T>C) pathogenic?

SETD1B p.Cys1007= (c.3021T>C) is classified Likely benign in SETD1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-09). Rare (popmax 0.217%, eas); Associated with SETD1B-related disorder.

What condition is associated with SETD1B p.Cys1007= (c.3021T>C)?

SETD1B p.Cys1007= (c.3021T>C) is associated with SETD1B-related disorder (ClinVar).

How common is SETD1B p.Cys1007= (c.3021T>C) in the general population?

SETD1B p.Cys1007= (c.3021T>C) is rare (popmax 0.217%, eas) (gnomAD).

SETD1B p.Cys1007=

c.3021T>C · rs555754128 · VCV3035467

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.217%, eas)

Conditions

SETD1B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -2.5
Overall
CADD	1.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.217% East Asian · 88/40,614 alleles

Filtering AF 0.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.00951% 146/1,535,728 alleles · rare exomes 132/1,383,428 · genomes 14/152,300 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.217%	462
Remaining individualsnot grpmax-eligible	0.0253%	3,951
South Asian	0.0194%	5,161
European (non-Finnish)	0.00238%	42,088

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: SETD1B
Protein: p.Cys1007=
Coding: c.3021T>C
MANE Select: NM_001353345
dbSNP: rs555754128
Type: single nucleotide variant
Location: chr12:121817413 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 1007: a UniProt-annotated variant site (in iddseld); the 'disordered' region

Full SETD1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SETD1B-related disorder

Similar variants

SETD1B p.Cys1007Arg Uncertain significance ★ ⚠ same residue
SETD1B p.Tyr1943Cys Pathogenic/Likely pathogenic ★★ same condition
SETD1B p.Phe546Leu Uncertain significance ★★ ⚠ same condition
SETD1B c.544+1G>A Likely pathogenic ★ same condition
SETD1B p.Asp1893Asn Likely pathogenic ★ same condition
SETD1B p.Asp1893His Likely pathogenic ★ same condition
SETD1B p.Ala1003Val Uncertain significance ★ ⚠ same condition
SETD1B p.Ala1636Pro 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/setd1b-p-cys1007 (accessed [today's date]).

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