Is SET p.Asp235Glu (c.705T>A) pathogenic?

SET p.Asp235Glu (c.705T>A) is classified Likely benign in SET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0981); Ultra-rare (popmax 0.0158%, eas); Associated with Inborn genetic diseases.

What condition is associated with SET p.Asp235Glu (c.705T>A)?

SET p.Asp235Glu (c.705T>A) is associated with Inborn genetic diseases (ClinVar).

How common is SET p.Asp235Glu (c.705T>A) in the general population?

SET p.Asp235Glu (c.705T>A) is ultra-rare (popmax 0.0158%, eas) (gnomAD).

What do computational predictors say about SET p.Asp235Glu (c.705T>A)?

AlphaMissense predicts likely benign (score 0.0981) — an in-silico prediction, not a clinical call.

SET p.Asp235Glu

c.705T>A · VCV3794570

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0981 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0981	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.42	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 0.14	GERP -0.099, phastCons 0.99
Regional constraint	o/e 0.70	unconstrained · MANE · 756 bp · p 0.017 · regional, not allelic
Overall
CADD	18.22	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 D248E vs ClinVar D235E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0158% East Asian · 7/44,350 alleles

Filtering AF 0.00873% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00943% 144/1,527,414 alleles · ultra-rare exomes 131/1,376,606 · genomes 13/150,808 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
East Asiangrpmax	0.0158%	6,336
Admixed American	0.0135%	7,386
European (non-Finnish)	0.0103%	9,688
Remaining individualsnot grpmax-eligible	0.0101%	9,933
African / African-American	0.00688%	14,545
South Asian	0.0034%	29,416

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SET
Protein: p.Asp235Glu
Coding: c.705T>A
MANE Select: NM_003011
Type: single nucleotide variant
Location: chr9:128693937 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 248 UniProt numbering: a UniProt-annotated variant site (in mrd58); the 'disordered' region

Full SET 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

SET p.Asp260Glu Uncertain significance ★★ ⚠ same condition
SET p.Glu261Asp Uncertain significance ★★ ⚠ same condition
SET c.492+4T>C Uncertain significance ★ same condition
SET p.Glu233Gly Uncertain significance ★ ⚠ same condition
SET p.Glu271Asp Uncertain significance ★ ⚠ same condition
SET p.Leu95Pro Uncertain significance ★ ⚠ same condition
SET p.Thr167Met Uncertain significance ★ ⚠ same condition
SET p.Thr173Met Likely benign ★ 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-asp235glu (accessed [today's date]).

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