Is SETD2 p.Asn801= (c.2403C>T) pathogenic?

SETD2 p.Asn801= (c.2403C>T) is classified Likely benign in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). Ultra-rare (popmax 0.0105%, nfe); Associated with Luscan-Lumish syndrome.

What condition is associated with SETD2 p.Asn801= (c.2403C>T)?

SETD2 p.Asn801= (c.2403C>T) is associated with Luscan-Lumish syndrome (ClinVar).

How common is SETD2 p.Asn801= (c.2403C>T) in the general population?

SETD2 p.Asn801= (c.2403C>T) is ultra-rare (popmax 0.0105%, nfe) (gnomAD).

SETD2 p.Asn801=

c.2403C>T · rs200127446 · VCV775021

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, nfe)

Conditions

Luscan-Lumish syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.4, phastCons 0.84
Overall
CADD	4.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% European (non-Finnish) · 124/1,180,004 alleles

Filtering AF 0.00891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00842%

Overall 0.00849% 137/1,613,988 alleles · ultra-rare exomes 130/1,461,784 · genomes 7/152,204 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)grpmax	0.0105%	9,516
African / African-American	0.00534%	18,732
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Admixed American	0.00167%	59,996

Remaining individuals 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: SETD2
Protein: p.Asn801=
Coding: c.2403C>T
MANE Select: NM_014159
dbSNP: rs200127446
Type: single nucleotide variant
Location: chr3:47122233 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 801: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation)

Full SETD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Luscan-Lumish syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD2 p.Asn801Ser Benign ★ same residue
SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same condition
SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same condition
SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same condition
SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same condition
SETD2 p.Ala679Val Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg1065Cys Uncertain significance ★★ same condition
SETD2 p.Arg329Gln 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/setd2-p-asn801 (accessed [today's date]).

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