Is SETBP1 p.Ser172fs (c.514dup) pathogenic?

SETBP1 p.Ser172fs (c.514dup) is classified Pathogenic in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-04). No gnomAD frequency available for this variant.

How common is SETBP1 p.Ser172fs (c.514dup) in the general population?

SETBP1 p.Ser172fs (c.514dup) is no gnomAD frequency available for this variant (gnomAD).

SETBP1 p.Ser172fs

c.514dup · rs2511247912 · VCV2014025

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SETBP1
Protein: p.Ser172fs
Coding: c.514dup
MANE Select: NM_015559
dbSNP: rs2511247912
Type: Duplication
Location: chr18:44869256 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 172: the 'disordered' region

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

Similar variants

SETBP1 p.Ser172Arg Uncertain significance ★ ⚠ same residue
SETBP1 p.Ser172= Likely benign ★ same residue
SETBP1 p.Ser172Asn Benign ★ same residue
SETBP1 p.Glu16fs Pathogenic ★★ same type
SETBP1 p.Arg1549fs Uncertain significance ★★ same type
SETBP1 p.Ala1245fs Pathogenic ★ same type
SETBP1 p.Asn147fs Pathogenic ★ same type
SETBP1 p.Asn913fs 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-ser172fs (accessed [today's date]).

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