Is SETBP1 p.Pro612Ser (c.1834C>T) pathogenic?

SETBP1 p.Pro612Ser (c.1834C>T) is classified Uncertain significance in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-02). AlphaMissense: likely pathogenic (0.7852); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SETBP1 p.Pro612Ser (c.1834C>T)?

SETBP1 p.Pro612Ser (c.1834C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SETBP1 p.Pro612Ser (c.1834C>T) in the general population?

SETBP1 p.Pro612Ser (c.1834C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETBP1 p.Pro612Ser (c.1834C>T)?

AlphaMissense predicts likely pathogenic (score 0.7852) — an in-silico prediction, not a clinical call.

SETBP1 p.Pro612Ser

c.1834C>T · VCV4840853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7852	likely pathogenic
REVEL	0.338	indeterminate
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 158 bp · p 8e-08 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SETBP1
Protein: p.Pro612Ser
Coding: c.1834C>T
MANE Select: NM_015559
Type: single nucleotide variant
Location: chr18:44951174 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 612: the 'disordered' region

Full SETBP1 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

SETBP1 p.Arg589Ter Pathogenic ★★ same condition
SETBP1 p.Gln809Ter Pathogenic ★★ same condition
SETBP1 p.Glu858Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
SETBP1 p.Ala1366Ser Uncertain significance ★★ ⚠ same condition
SETBP1 p.Ala436Val Uncertain significance ★★ ⚠ same condition
SETBP1 p.Ala745Asp Uncertain significance ★★ ⚠ same condition
SETBP1 p.Arg143Gly Uncertain significance ★★ ⚠ same condition
SETBP1 p.Arg1485Thr 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/setbp1-p-pro612ser (accessed [today's date]).

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