Is SETD1B p.Ala1848= (c.5544G>A) pathogenic?

SETD1B p.Ala1848= (c.5544G>A) is classified Likely benign in SETD1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-11). Rare (popmax 0.18%, afr); Associated with Inborn genetic diseases.

What condition is associated with SETD1B p.Ala1848= (c.5544G>A)?

SETD1B p.Ala1848= (c.5544G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1B p.Ala1848= (c.5544G>A) in the general population?

SETD1B p.Ala1848= (c.5544G>A) is rare (popmax 0.18%, afr) (gnomAD).

SETD1B p.Ala1848=

c.5544G>A · rs375850421 · VCV3037247

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.18%, afr)

Conditions

Inborn genetic diseases

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 -10	GERP -3.9
Overall
CADD	0.489	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.18% African / African-American · 132/73,530 alleles

Filtering AF 0.155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.0091% 142/1,559,754 alleles · rare exomes 62/1,407,420 · genomes 80/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.18%	557
Middle Eastern	0.0167%	5,998
Admixed American	0.00959%	10,429
Remaining individualsnot grpmax-eligible	0.00331%	30,241
European (non-Finnish)	0.000174%	575,546

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.Ala1848=
Coding: c.5544G>A
MANE Select: NM_001353345
dbSNP: rs375850421
Type: single nucleotide variant
Location: chr12:121827809 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 1848: the set domain; a UniProt-annotated variant site (in iddseld)

Full SETD1B 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

SETD1B p.Ala1848Thr Uncertain significance ★ ⚠ same residue
SETD1B p.Ala1657Val Uncertain significance ★★ ⚠ same condition
SETD1B p.Ala654Thr Uncertain significance ★★ ⚠ same condition
SETD1B p.Arg1428Trp Uncertain significance ★★ ⚠ same condition
SETD1B p.Arg1458His Uncertain significance ★★ ⚠ same condition
SETD1B p.Arg1643His Uncertain significance ★★ ⚠ same condition
SETD1B p.Arg1670Gln Uncertain significance ★★ ⚠ same condition
SETD1B p.Arg467Gln 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-ala1848 (accessed [today's date]).

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