Is SETBP1 p.Ala770= (c.2310G>A) pathogenic?

SETBP1 p.Ala770= (c.2310G>A) is classified Benign/Likely benign in SETBP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-13). Rare (popmax 0.148%, mid); Associated with Schinzel-Giedion syndrome.

What condition is associated with SETBP1 p.Ala770= (c.2310G>A)?

SETBP1 p.Ala770= (c.2310G>A) is associated with Schinzel-Giedion syndrome (ClinVar).

How common is SETBP1 p.Ala770= (c.2310G>A) in the general population?

SETBP1 p.Ala770= (c.2310G>A) is rare (popmax 0.148%, mid) (gnomAD).

SETBP1 p.Ala770=

c.2310G>A · rs373845529 · VCV1632076

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Conditions

Schinzel-Giedion syndrome

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 -2.3	GERP -5.7
Overall
CADD	4.404	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.0173% 280/1,614,138 alleles · rare exomes 256/1,461,886 · genomes 24/152,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
Admixed American	0.0533%	1,876
African / African-American	0.0267%	3,752
South Asian	0.0264%	3,795
Remaining individualsnot grpmax-eligible	0.024%	4,167
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935
European (non-Finnish)	0.0145%	6,901
East Asian	0.00669%	14,956

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: SETBP1
Protein: p.Ala770=
Coding: c.2310G>A
MANE Select: NM_015559
dbSNP: rs373845529
Type: single nucleotide variant
Location: chr18:44951650 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30

Full SETBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Schinzel-Giedion syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETBP1 p.Ala770Gly Uncertain significance ★★ ⚠ same residue
SETBP1 p.Ala770Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SETBP1 p.Ala770Val Uncertain significance ★ ⚠ same residue
SETBP1 p.Arg589Ter Pathogenic ★★ same condition
SETBP1 p.Arg625Ter Pathogenic ★★ same condition
SETBP1 p.Arg626Ter Pathogenic ★★ same condition
SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same condition
SETBP1 p.Asp868His 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/setbp1-p-ala770 (accessed [today's date]).

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