Is UNC80 p.Pro381Ser (c.1141C>T) pathogenic?

UNC80 p.Pro381Ser (c.1141C>T) is classified Uncertain significance in UNC80 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.7239); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with UNC80 p.Pro381Ser (c.1141C>T)?

UNC80 p.Pro381Ser (c.1141C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC80 p.Pro381Ser (c.1141C>T) in the general population?

UNC80 p.Pro381Ser (c.1141C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC80 p.Pro381Ser (c.1141C>T)?

AlphaMissense predicts likely pathogenic (score 0.7239) — an in-silico prediction, not a clinical call.

UNC80 p.Pro381Ser

c.1141C>T · rs2079532343 · VCV2120739

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7239 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7239	likely pathogenic
REVEL	0.157	moderately 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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 57 kb · p 0.0051 · regional, not allelic
Overall
CADD	23.9	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

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.Pro381Ser
Coding: c.1141C>T
MANE Select: NM_001371986
dbSNP: rs2079532343
Type: single nucleotide variant
Location: chr2:209813782 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC80 p.Ala1338Ser Uncertain significance ★★ same condition
UNC80 p.Ala1886Thr Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala1907Thr Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala2284Val Uncertain significance ★★ same condition
UNC80 p.Ala537Thr Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala676Gly Uncertain significance ★★ same condition
UNC80 p.Ala864Gly Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala977Thr Uncertain significance ★★ ⚠ 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-pro381ser (accessed [today's date]).

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