Is UNC80 p.Thr3003Ser (c.9008C>G) pathogenic?

UNC80 p.Thr3003Ser (c.9008C>G) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-04). AlphaMissense: likely pathogenic (0.608); Absent from gnomAD v4.1.

How common is UNC80 p.Thr3003Ser (c.9008C>G) in the general population?

UNC80 p.Thr3003Ser (c.9008C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC80 p.Thr3003Ser (c.9008C>G)?

AlphaMissense predicts likely pathogenic (score 0.608) — an in-silico prediction, not a clinical call.

UNC80 p.Thr3003Ser

c.9008C>G · rs2125019220 · VCV1362487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.608 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.608	likely pathogenic
REVEL	0.25	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 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 16 kb · p 0.061 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T2937S vs ClinVar T3003S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UNC80
Protein: p.Thr3003Ser
Coding: c.9008C>G
MANE Select: NM_001371986
dbSNP: rs2125019220
Type: single nucleotide variant
Location: chr2:209978598 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Similar variants

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
UNC80 p.Arg1179Ter Pathogenic/Likely pathogenic ★★ same type
UNC80 p.Arg1285Ter 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-thr3003ser (accessed [today's date]).

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