Is SETBP1 p.Arg11Trp (c.31C>T) pathogenic?

SETBP1 p.Arg11Trp (c.31C>T) is classified Likely benign in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-08). AlphaMissense: likely benign (0.235); Ultra-rare (popmax 0.017%, mid).

How common is SETBP1 p.Arg11Trp (c.31C>T) in the general population?

SETBP1 p.Arg11Trp (c.31C>T) is ultra-rare (popmax 0.017%, mid) (gnomAD).

What do computational predictors say about SETBP1 p.Arg11Trp (c.31C>T)?

AlphaMissense predicts likely benign (score 0.235) — an in-silico prediction, not a clinical call.

SETBP1 p.Arg11Trp

c.31C>T · rs776221622 · VCV1431766

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.235 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.235	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 232 bp · p 0.68 · regional, not allelic
Overall
CADD	25.5	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 0.017% Middle Eastern · 1/5,878 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000324%

Overall 0.000913% 14/1,533,376 alleles · ultra-rare exomes 13/1,381,294 · genomes 1/152,082 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,878
East Asian	0.00245%	40,836
Admixed American	0.00203%	49,300
Remaining individualsnot grpmax-eligible	0.00169%	59,076
European (non-Finnish)	0.000879%	113,705

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.Arg11Trp
Coding: c.31C>T
MANE Select: NM_015559
dbSNP: rs776221622
Type: single nucleotide variant
Location: chr18:44701377 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 11: the 'disordered' region

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

Similar variants

SETBP1 p.Arg11Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
SETBP1 p.Arg11Gly Uncertain significance ★ same residue
SETBP1 p.Arg530Ter Pathogenic ★★ same type
SETBP1 p.Arg544Ter Pathogenic/Likely pathogenic ★★ same type
SETBP1 p.Arg589Ter Pathogenic ★★ same type
SETBP1 p.Arg625Ter Pathogenic ★★ same type
SETBP1 p.Arg626Ter Pathogenic ★★ same type
SETBP1 p.Arg889Ter 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-arg11trp (accessed [today's date]).

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