Is SETD2 p.Ser2238fs (c.6712_6718del) pathogenic?

SETD2 p.Ser2238fs (c.67126718del) is classified Pathogenic in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-02). No gnomAD frequency available for this variant; Associated with Luscan-Lumish syndrome.

What condition is associated with SETD2 p.Ser2238fs (c.6712_6718del)?

SETD2 p.Ser2238fs (c.6712_6718del) is associated with Luscan-Lumish syndrome (ClinVar).

How common is SETD2 p.Ser2238fs (c.6712_6718del) in the general population?

SETD2 p.Ser2238fs (c.6712_6718del) is no gnomAD frequency available for this variant (gnomAD).

SETD2 p.Ser2238fs

c.6712_6718del · rs2107575654 · VCV1320096

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Luscan-Lumish syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 15 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: SETD2
Protein: p.Ser2238fs
Coding: c.6712_6718del
MANE Select: NM_014159
dbSNP: rs2107575654
Type: Deletion
Location: chr3:47057066 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 2238: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'low charge region' region

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 c.5015+39_5015+40del Benign ★★ same condition
SETD2 c.6110-27_6110-26del Benign/Likely benign ★★ same condition
SETD2 p.Gly1726fs Pathogenic ★ same condition
SETD2 p.Lys1486fs Pathogenic ★ same condition
SETD2 p.Gln2334_Ile2336del Uncertain significance ★ same condition
SETD2 p.Ser1268del Uncertain significance ★ same condition
SETD2 p.Ser2271del Uncertain significance ★ same condition
SETD2 c.5398-13del 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/setd2-p-ser2238fs (accessed [today's date]).

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