Is SETBP1 p.Ala263Val (c.788C>T) pathogenic?

SETBP1 p.Ala263Val (c.788C>T) is classified Likely benign in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.0763); Very rare (popmax 0.00133%, afr).

How common is SETBP1 p.Ala263Val (c.788C>T) in the general population?

SETBP1 p.Ala263Val (c.788C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about SETBP1 p.Ala263Val (c.788C>T)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

SETBP1 p.Ala263Val

c.788C>T · rs752490647 · VCV2148660

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.13, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 249 kb · p 0.047 · regional, not allelic
Overall
CADD	20.5	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 0.00133% African / African-American · 1/74,932 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000806% 13/1,613,802 alleles · very rare exomes 12/1,461,626 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,932
European (non-Finnish)	0.00102%	98,337

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.Ala263Val
Coding: c.788C>T
MANE Select: NM_015559
dbSNP: rs752490647
Type: single nucleotide variant
Location: chr18:44950128 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 263: the 'disordered' region

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

Similar variants

SETBP1 p.Arg530Ter Pathogenic ★★ same type
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SETBP1 p.Arg589Ter Pathogenic ★★ same type
SETBP1 p.Arg625Ter Pathogenic ★★ same type
SETBP1 p.Arg626Ter Pathogenic ★★ same type
SETBP1 p.Arg889Ter Pathogenic ★★ same type
SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same type
SETBP1 p.Asp868His Pathogenic/Likely pathogenic ★★ ⚠ same type

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-ala263val (accessed [today's date]).

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