Is UNC80 p.Arg1069Leu (c.3206G>T) pathogenic?

UNC80 p.Arg1069Leu (c.3206G>T) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-19). AlphaMissense: likely pathogenic (0.9445); No allele count reported in gnomAD v4.1 (AN 1,552,010).

How common is UNC80 p.Arg1069Leu (c.3206G>T) in the general population?

UNC80 p.Arg1069Leu (c.3206G>T) is no allele count reported in gnomAD v4.1 (AN 1,552,010) (gnomAD).

What do computational predictors say about UNC80 p.Arg1069Leu (c.3206G>T)?

AlphaMissense predicts likely pathogenic (score 0.9445) — an in-silico prediction, not a clinical call.

UNC80 p.Arg1069Leu

c.3206G>T · VCV4959589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9445 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,010)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.9445	likely pathogenic
REVEL	0.257	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,552,010). 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.Arg1069Leu
Coding: c.3206G>T
MANE Select: NM_001371986
Type: single nucleotide variant
Location: chr2:209839386 (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.Arg1069Ter Pathogenic ★★ same residue
UNC80 p.Arg1069Gln 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-arg1069leu (accessed [today's date]).

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