Is SETD5 p.Val473fs (c.1416dup) pathogenic?

SETD5 p.Val473fs (c.1416dup) is classified Pathogenic in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-28). No gnomAD frequency available for this variant; Associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency.

How common is SETD5 p.Val473fs (c.1416dup) in the general population?

SETD5 p.Val473fs (c.1416dup) is no gnomAD frequency available for this variant (gnomAD).

SETD5 p.Val473fs

Q: What condition is associated with SETD5 p.Val473fs (c.1416dup)?

SETD5 p.Val473fs (c.1416dup) is associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (ClinVar).

c.1416dup · rs2472832047 · VCV1992342

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

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 12 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, 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.Val473fs
Coding: c.1416dup
MANE Select: NM_001080517
dbSNP: rs2472832047
Type: Duplication
Location: chr3:9445271 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 473: 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.Tyr1000fs Pathogenic/Likely pathogenic ★★ same condition
SETD5 p.Ala647fs Likely pathogenic ★ same condition
SETD5 p.Asn1059fs Likely pathogenic ★ same condition
SETD5 p.Asn814fs Pathogenic ★ same condition
SETD5 p.Gln534fs Likely pathogenic ★ same condition
SETD5 p.Gln801fs Pathogenic ★ same condition
SETD5 p.Gly344fs Pathogenic ★ same condition
SETD5 p.His966fs 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-val473fs (accessed [today's date]).

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