Is SETBP1 p.Ser567Phe (c.1700C>T) pathogenic?

SETBP1 p.Ser567Phe (c.1700C>T) is classified Likely benign in SETBP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.9285); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with SETBP1 p.Ser567Phe (c.1700C>T)?

SETBP1 p.Ser567Phe (c.1700C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SETBP1 p.Ser567Phe (c.1700C>T) in the general population?

SETBP1 p.Ser567Phe (c.1700C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about SETBP1 p.Ser567Phe (c.1700C>T)?

AlphaMissense predicts likely pathogenic (score 0.9285) — an in-silico prediction, not a clinical call.

SETBP1 p.Ser567Phe

c.1700C>T · rs966735327 · VCV1493881

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9285 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9285	likely pathogenic
REVEL	0.394	indeterminate
SaProt	LLR -8.37	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	27.5	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 0.0156% East Asian · 7/44,864 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000558% 9/1,613,978 alleles · ultra-rare exomes 8/1,461,858 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Ser567Phe
Coding: c.1700C>T
MANE Select: NM_015559
dbSNP: rs966735327
Type: single nucleotide variant
Location: chr18:44951040 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETBP1 p.Ser567Cys Uncertain significance ★ same residue
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

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-ser567phe (accessed [today's date]).

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