Is SET p.Ala20Val (c.59C>T) pathogenic?

SET p.Ala20Val (c.59C>T) is classified Likely benign in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-18). No allele count reported in gnomAD v4.1 (AN 1,314,986); Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Ala20Val (c.59C>T)?

SET p.Ala20Val (c.59C>T) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

How common is SET p.Ala20Val (c.59C>T) in the general population?

SET p.Ala20Val (c.59C>T) is no allele count reported in gnomAD v4.1 (AN 1,314,986) (gnomAD).

SET p.Ala20Val

c.59C>T · VCV4851388

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,314,986)

Conditions

intellectual disability, autosomal dominant 58

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.123	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.8	GERP 0.27, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 60 bp · p 0.41 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,314,986). 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: SET
Protein: p.Ala20Val
Coding: c.59C>T
MANE Select: NM_003011
Type: single nucleotide variant
Location: chr9:128689641 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 20: the 'disordered' region

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

Disease context

intellectual disability, autosomal dominant 58 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SET c.663+5G>C Pathogenic ★★ same condition
SET p.His105Tyr Likely pathogenic ★★ same condition
SET p.Asp224Asn Uncertain significance ★★ ⚠ same condition
SET p.Asp260Glu Uncertain significance ★★ ⚠ same condition
SET p.Glu261Asp Uncertain significance ★★ ⚠ same condition
SET c.132-17C>T Benign ★★ same condition
SET c.493-14C>T Benign ★★ same condition
SET c.493-1G>A Pathogenic ★ 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/set-p-ala20val (accessed [today's date]).

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