Is UNC80 p.Arg1069Ter (c.3205C>T) pathogenic?

UNC80 p.Arg1069Ter (c.3205C>T) is classified Pathogenic in UNC80 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Very rare (popmax 0.00392%, amr).

How common is UNC80 p.Arg1069Ter (c.3205C>T) in the general population?

UNC80 p.Arg1069Ter (c.3205C>T) is very rare (popmax 0.00392%, amr) (gnomAD).

UNC80 p.Arg1069Ter

c.3205C>T · rs754371531 · VCV2662943

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

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 19 of 65
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -1.5, phastCons 0.026
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 0.00392% Admixed American · 2/50,984 alleles

Filtering AF 0.00065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000193% 3/1,551,924 alleles · very rare exomes 2/1,399,834 · genomes 1/152,090 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00392%	25,492
European (non-Finnish)	8.72e-05%	1,147,076

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.Arg1069Ter
Coding: c.3205C>T
MANE Select: NM_001371986
dbSNP: rs754371531
Type: single nucleotide variant
Location: chr2:209839385 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1069: the 'disordered' region

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

Similar variants

UNC80 p.Arg1069Gln Uncertain significance ★ ⚠ same residue
UNC80 p.Arg1069Leu Uncertain significance ★ ⚠ same residue
UNC80 c.4110+1G>C Pathogenic/Likely pathogenic ★★ same type
UNC80 c.7287-1G>A Likely pathogenic ★★ same type
UNC80 c.8772+1G>A Likely pathogenic ★★ same type
UNC80 p.Arg1076Ter Pathogenic ★★ same type
UNC80 p.Arg1110Ter Pathogenic ★★ same type
UNC80 p.Arg1179Ter Pathogenic/Likely pathogenic ★★ same type

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-arg1069ter (accessed [today's date]).

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