Is SETD1B p.Pro1479Ser (c.4435C>T) pathogenic?

SETD1B p.Pro1479Ser (c.4435C>T) is classified Uncertain significance in SETD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). AlphaMissense: likely benign (0.1606); Ultra-rare (popmax 0.0141%, amr); Associated with Inborn genetic diseases.

What condition is associated with SETD1B p.Pro1479Ser (c.4435C>T)?

SETD1B p.Pro1479Ser (c.4435C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1B p.Pro1479Ser (c.4435C>T) in the general population?

SETD1B p.Pro1479Ser (c.4435C>T) is ultra-rare (popmax 0.0141%, amr) (gnomAD).

What do computational predictors say about SETD1B p.Pro1479Ser (c.4435C>T)?

AlphaMissense predicts likely benign (score 0.1606) — an in-silico prediction, not a clinical call.

SETD1B p.Pro1479Ser

c.4435C>T · VCV3440166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1606 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1606	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -10.05	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,108 bp · p 0.69 · regional, not allelic
Overall
CADD	16.97	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 0.0141% Admixed American · 7/49,696 alleles

Filtering AF 0.00653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00464%

Overall 0.000591% 9/1,521,664 alleles · ultra-rare exomes 4/1,369,754 · genomes 5/151,910 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0141%	7,099
Ashkenazi Jewishnot grpmax-eligible	0.00365%	27,384
Remaining individualsnot grpmax-eligible	0.00169%	59,238

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.Pro1479Ser
Coding: c.4435C>T
MANE Select: NM_001353345
Type: single nucleotide variant
Location: chr12:121823014 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 1479: 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.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
SETD1B p.Asp1107Asn 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-pro1479ser (accessed [today's date]).

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