Is UNC80 p.Arg1007Cys (c.3019C>T) pathogenic?

UNC80 p.Arg1007Cys (c.3019C>T) is classified Uncertain significance in UNC80 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-05). AlphaMissense: likely benign (0.1609); Very rare (popmax 0.00238%, sas).

How common is UNC80 p.Arg1007Cys (c.3019C>T) in the general population?

UNC80 p.Arg1007Cys (c.3019C>T) is very rare (popmax 0.00238%, sas) (gnomAD).

What do computational predictors say about UNC80 p.Arg1007Cys (c.3019C>T)?

AlphaMissense predicts likely benign (score 0.1609) — an in-silico prediction, not a clinical call.

UNC80 p.Arg1007Cys

c.3019C>T · rs1337125361 · VCV1364550

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1609 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1609	likely benign
REVEL	0.253	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.33	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% South Asian · 2/83,950 alleles

Filtering AF 0.000395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000148%

Overall 0.000258% 4/1,550,688 alleles · very rare exomes 4/1,398,424 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00238%	41,975
European (non-Finnish)	0.000174%	573,161

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.Arg1007Cys
Coding: c.3019C>T
MANE Select: NM_001371986
dbSNP: rs1337125361
Type: single nucleotide variant
Location: chr2:209834988 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1007: the 'disordered' region

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

Similar variants

UNC80 p.Arg1007His Uncertain significance ★★ ⚠ same residue
UNC80 p.Arg1007Pro 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.Arg1069Ter Pathogenic ★★ same type
UNC80 p.Arg1076Ter Pathogenic ★★ same type
UNC80 p.Arg1110Ter 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-arg1007cys (accessed [today's date]).

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