Is UNC80 p.Arg360Ter (c.1078C>T) pathogenic?

UNC80 p.Arg360Ter (c.1078C>T) is classified Pathogenic/Likely pathogenic in UNC80 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-02-13). Very rare (popmax 0.00137%, afr); Associated with UNC80-related disorder.

What condition is associated with UNC80 p.Arg360Ter (c.1078C>T)?

UNC80 p.Arg360Ter (c.1078C>T) is associated with UNC80-related disorder, hypotonia, infantile, with psychomotor retardation and characteristic facies 2 (ClinVar).

How common is UNC80 p.Arg360Ter (c.1078C>T) in the general population?

UNC80 p.Arg360Ter (c.1078C>T) is very rare (popmax 0.00137%, afr) (gnomAD).

UNC80 p.Arg360Ter

c.1078C>T · rs200659479 · VCV219189

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Conditions

UNC80-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 65
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.12	GERP -2.5, phastCons 0.23
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/72,990 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000387% 6/1,551,580 alleles · very rare exomes 5/1,399,514 · genomes 1/152,066 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	72,990
European (non-Finnish)	0.000436%	229,401

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: UNC80
Protein: p.Arg360Ter
Coding: c.1078C>T
MANE Select: NM_001371986
dbSNP: rs200659479
Type: single nucleotide variant
Location: chr2:209813719 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 360: an α-helix

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

Disease context

UNC80-related disorder

Also linked: hypotonia, infantile, with psychomotor retardation and characteristic facies 2

Similar variants

UNC80 p.Arg360Gln Uncertain significance ★ ⚠ same residue
UNC80 p.Arg360Leu Conflicting classifications of pathogenicity ★ same residue
UNC80 p.Arg360Pro Uncertain significance ★ same residue
UNC80 p.Arg360= Likely benign ★ same residue
UNC80 c.4110+1G>C Pathogenic/Likely pathogenic ★★ same condition
UNC80 c.8772+1G>A Likely pathogenic ★★ same condition
UNC80 p.Arg1076Ter Pathogenic ★★ same condition
UNC80 p.Arg1110Ter 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-arg360ter (accessed [today's date]).

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