Is SET p.Asn40Ser (c.119A>G) pathogenic?

SET p.Asn40Ser (c.119A>G) is classified Uncertain significance in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-27). AlphaMissense: ambiguous (0.4995); Absent from gnomAD v4.1.

How common is SET p.Asn40Ser (c.119A>G) in the general population?

SET p.Asn40Ser (c.119A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SET p.Asn40Ser (c.119A>G)?

AlphaMissense predicts ambiguous (score 0.4995) — an in-silico prediction, not a clinical call.

SET p.Asn40Ser

c.119A>G · VCV3392958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4995	ambiguous
REVEL	0.202	benign-leaning
SaProt	LLR -10.68	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 4,260 bp · p 5.8e-31 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N53S vs ClinVar N40S) — verify the residue.

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: SET
Protein: p.Asn40Ser
Coding: c.119A>G
MANE Select: NM_003011
Type: single nucleotide variant
Location: chr9:128691215 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 53 UniProt numbering: an α-helix; the 'dimerization' region

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

Similar variants

SET c.663+5G>C Pathogenic ★★ same type
SET p.His105Tyr Likely pathogenic ★★ same type
SET p.Asp224Asn Uncertain significance ★★ ⚠ same type
SET p.Asp260Glu Uncertain significance ★★ ⚠ same type
SET p.Glu261Asp Uncertain significance ★★ ⚠ same type
SET p.Phe189Cys Uncertain significance ★★ ⚠ same type
SET c.132-17C>T Benign ★★ same type
SET c.493-14C>T Benign ★★ 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/set-p-asn40ser (accessed [today's date]).

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