Is UNC80 p.Arg453fs (c.1357del) pathogenic?

UNC80 p.Arg453fs (c.1357del) is classified Pathogenic/Likely pathogenic in UNC80 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-01). No gnomAD frequency available for this variant; Associated with hypotonia, infantile, with psychomotor retardation and characteristic facies 2.

What condition is associated with UNC80 p.Arg453fs (c.1357del)?

UNC80 p.Arg453fs (c.1357del) is associated with hypotonia, infantile, with psychomotor retardation and characteristic facies 2 (ClinVar).

How common is UNC80 p.Arg453fs (c.1357del) in the general population?

UNC80 p.Arg453fs (c.1357del) is no gnomAD frequency available for this variant (gnomAD).

UNC80 p.Arg453fs

Q: How is Hypotonia-speech impairment-severe cognitive delay syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1357del · rs1574574226 · VCV829816

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypotonia, infantile, with psychomotor retardation and characteristic facies 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 65
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, 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: UNC80
Protein: p.Arg453fs
Coding: c.1357del
MANE Select: NM_001371986
dbSNP: rs1574574226
Type: Deletion
Location: chr2:209816929 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 453: the 'disordered' region

Full UNC80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypotonia, infantile, with psychomotor retardation and characteristic facies 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypotonia-speech impairment-severe cognitive delay syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

UNC80 p.Lys2924fs Pathogenic ★★ same condition
UNC80 p.Thr2567fs Pathogenic/Likely pathogenic ★★ same condition
UNC80 p.Tyr355fs Likely pathogenic ★★ same condition
UNC80 c.6646+1del Pathogenic ★ same condition
UNC80 p.Ala2353fs Pathogenic ★ same condition
UNC80 p.Arg453Ter Pathogenic ★ same residue
UNC80 p.Asn678fs Likely pathogenic ★ same condition
UNC80 p.Leu3118fs 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/unc80-p-arg453fs (accessed [today's date]).

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