Is SETD5 p.Asp499fs (c.1495del) pathogenic?

SETD5 p.Asp499fs (c.1495del) is classified Pathogenic in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-15). No gnomAD frequency available for this variant; Associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency.

How common is SETD5 p.Asp499fs (c.1495del) in the general population?

SETD5 p.Asp499fs (c.1495del) is no gnomAD frequency available for this variant (gnomAD).

SETD5 p.Asp499fs

Q: What condition is associated with SETD5 p.Asp499fs (c.1495del)?

SETD5 p.Asp499fs (c.1495del) is associated with intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (ClinVar).

c.1495del · rs2041856807 · VCV1032603

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 13 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.36	GERP -2, 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.Asp499fs
Coding: c.1495del
MANE Select: NM_001080517
dbSNP: rs2041856807
Type: Deletion
Location: chr3:9445711 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 499: 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.Gln224fs Pathogenic ★★ same condition
SETD5 p.Ser1286fs Pathogenic/Likely pathogenic ★★ same condition
SETD5 p.Asp499Tyr Uncertain significance ★★ ⚠ same residue
SETD5 p.Ala641fs Likely pathogenic ★ same condition
SETD5 p.Arg290fs Pathogenic ★ same condition
SETD5 p.Arg589fs Pathogenic ★ same condition
SETD5 p.Asn345fs Pathogenic ★ same condition
SETD5 p.Asn573fs 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-asp499fs (accessed [today's date]).

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