Is SETD1B p.Phe1903Val (c.5707T>G) pathogenic?

SETD1B p.Phe1903Val (c.5707T>G) is classified Likely pathogenic in SETD1B (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9993); No allele count reported in gnomAD v4.1 (AN 1,552,284); Associated with intellectual developmental disorder with seizures and language delay.

What condition is associated with SETD1B p.Phe1903Val (c.5707T>G)?

SETD1B p.Phe1903Val (c.5707T>G) is associated with intellectual developmental disorder with seizures and language delay (ClinVar).

How common is SETD1B p.Phe1903Val (c.5707T>G) in the general population?

SETD1B p.Phe1903Val (c.5707T>G) is no allele count reported in gnomAD v4.1 (AN 1,552,284) (gnomAD).

What do computational predictors say about SETD1B p.Phe1903Val (c.5707T>G)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

SETD1B p.Phe1903Val

c.5707T>G · VCV4890781

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,284)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder with seizures and language delay

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 3% in SETD1B
REVEL	0.906	moderately pathogenic-leaning
SaProt	LLR -14.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 2,117 bp · p 1.3e-12 · regional, not allelic
Overall
CADD	26.8	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

No allele count reported in gnomAD v4.1 (AN 1,552,284). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SETD1B
Protein: p.Phe1903Val
Coding: c.5707T>G
MANE Select: NM_001353345
Type: single nucleotide variant
Location: chr12:121828050 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 1903: 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

intellectual developmental disorder with seizures and language delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD1B p.Arg1329Ter Pathogenic ★★ same condition
SETD1B p.Arg1703Ter Pathogenic/Likely pathogenic ★★ same condition
SETD1B p.Arg1748Cys Pathogenic/Likely pathogenic ★★ same condition
SETD1B p.Arg1792Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SETD1B p.Arg1825Trp Likely pathogenic ★★ same condition
SETD1B p.Arg1902Cys Pathogenic/Likely pathogenic ★★ same condition
SETD1B p.Gln780Ter Pathogenic/Likely pathogenic ★★ same condition
SETD1B p.Glu1948Lys Pathogenic/Likely pathogenic ★★ 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-phe1903val (accessed [today's date]).

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