Is SETD1B p.Ser826= (c.2478C>T) pathogenic?

SETD1B p.Ser826= (c.2478C>T) is classified Benign in SETD1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-28). Low-frequency (popmax 1.97%, afr); Associated with SETD1B-related disorder.

What condition is associated with SETD1B p.Ser826= (c.2478C>T)?

SETD1B p.Ser826= (c.2478C>T) is associated with SETD1B-related disorder (ClinVar).

How common is SETD1B p.Ser826= (c.2478C>T) in the general population?

SETD1B p.Ser826= (c.2478C>T) is low-frequency (popmax 1.97%, afr) (gnomAD).

SETD1B p.Ser826=

c.2478C>T · rs78876751 · VCV3050441

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.97%, afr)

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 -9.6	GERP -2.9
Overall
CADD	0.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.97% African / African-American · 1,442/73,120 alleles

Filtering AF 1.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.85%

Overall 0.105% 1,629/1,550,458 alleles · low-frequency exomes 771/1,398,296 · genomes 858/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.97%	51
Remaining individualsnot grpmax-eligible	0.135%	742
Admixed American	0.104%	962
Middle Eastern	0.0501%	1,996
Finnishnot grpmax-eligible	0.0374%	2,676
South Asian	0.00238%	42,029
European (non-Finnish)	0.00227%	44,113

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.Ser826=
Coding: c.2478C>T
MANE Select: NM_001353345
dbSNP: rs78876751
Type: single nucleotide variant
Location: chr12:121814693 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB

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

Disease context

SETD1B-related disorder

Similar variants

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
SETD1B p.Ala431Val 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-ser826 (accessed [today's date]).

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