Is SETD1B p.Val357= (c.1071C>T) pathogenic?

SETD1B p.Val357= (c.1071C>T) is classified Likely benign in SETD1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-26). Ultra-rare (popmax 0.069%, sas); Associated with Inborn genetic diseases.

What condition is associated with SETD1B p.Val357= (c.1071C>T)?

SETD1B p.Val357= (c.1071C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1B p.Val357= (c.1071C>T) in the general population?

SETD1B p.Val357= (c.1071C>T) is ultra-rare (popmax 0.069%, sas) (gnomAD).

SETD1B p.Val357=

c.1071C>T · rs760230171 · VCV2643423

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.069%, sas)

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 -2.7	GERP -3.2
Overall
CADD	0.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.069% South Asian · 58/84,054 alleles

Filtering AF 0.0547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0496%

Overall 0.01% 155/1,550,384 alleles · ultra-rare exomes 141/1,398,246 · genomes 14/152,138 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.069%	1,449
Middle Eastern	0.0166%	6,014
Remaining individualsnot grpmax-eligible	0.015%	6,675
European (non-Finnish)	0.00724%	13,818
Admixed American	0.00392%	25,491
East Asian	0.00244%	40,912
African / African-American	0.00137%	73,036

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.Val357=
Coding: c.1071C>T
MANE Select: NM_001353345
dbSNP: rs760230171
Type: single nucleotide variant
Location: chr12:121810016 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 357: the 'disordered' region

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-val357 (accessed [today's date]).

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