Is SETD5 p.Ser568fs (c.1702_1703insT) pathogenic?

SETD5 p.Ser568fs (c.17021703insT) is classified Pathogenic in SETD5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-31). No gnomAD frequency available for this variant; Associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency.

What condition is associated with SETD5 p.Ser568fs (c.1702_1703insT)?

SETD5 p.Ser568fs (c.1702_1703insT) is associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (ClinVar).

How common is SETD5 p.Ser568fs (c.1702_1703insT) in the general population?

SETD5 p.Ser568fs (c.1702_1703insT) is no gnomAD frequency available for this variant (gnomAD).

SETD5 p.Ser568fs

c.1702_1703insT · rs2042123799 · VCV998029

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency

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 14 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 0.77, 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: SETD5
Protein: p.Ser568fs
Coding: c.1702_1703insT
MANE Select: NM_001080517
dbSNP: rs2042123799
Type: Insertion
Location: chr3:9447227 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 568: the 'disordered' region; a UniProt-annotated variant site (in mrd23)

Full SETD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD5 p.Glu481delinsAlaTer Likely pathogenic ★ same condition
SETD5 p.Glu523fs Pathogenic ★ same condition
SETD5 p.Arg632fs Pathogenic same condition
SETD5 c.1441-1G>A Pathogenic ★★ same condition
SETD5 c.1525-1G>C Pathogenic/Likely pathogenic ★★ same condition
SETD5 c.2347-7A>G Pathogenic ★★ same condition
SETD5 c.3631+1G>A Pathogenic ★★ same condition
SETD5 c.960-5C>G Pathogenic/Likely 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/setd5-p-ser568fs (accessed [today's date]).

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