Is SETBP1 p.Val342Met (c.1024G>A) pathogenic?

SETBP1 p.Val342Met (c.1024G>A) is classified Uncertain significance in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-27). AlphaMissense: likely benign (0.0664); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SETBP1 p.Val342Met (c.1024G>A)?

SETBP1 p.Val342Met (c.1024G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SETBP1 p.Val342Met (c.1024G>A) in the general population?

SETBP1 p.Val342Met (c.1024G>A) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about SETBP1 p.Val342Met (c.1024G>A)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

SETBP1 p.Val342Met

c.1024G>A · VCV3794572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.55	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 3.2	GERP -0.26, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 249 kb · p 0.047 · regional, not allelic
Overall
CADD	16.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,048 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 19/1,461,780 alleles · very rare

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.Val342Met
Coding: c.1024G>A
MANE Select: NM_015559
Type: single nucleotide variant
Location: chr18:44950364 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 342: 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-val342met (accessed [today's date]).

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