Is UNC80 p.Pro1823Ser (c.5467C>T) pathogenic?

UNC80 p.Pro1823Ser (c.5467C>T) is classified Uncertain significance in UNC80 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-05). AlphaMissense: ambiguous (0.3636); Very rare (popmax 0.00274%, afr); Associated with Inborn genetic diseases.

What condition is associated with UNC80 p.Pro1823Ser (c.5467C>T)?

UNC80 p.Pro1823Ser (c.5467C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC80 p.Pro1823Ser (c.5467C>T) in the general population?

UNC80 p.Pro1823Ser (c.5467C>T) is very rare (popmax 0.00274%, afr) (gnomAD).

What do computational predictors say about UNC80 p.Pro1823Ser (c.5467C>T)?

AlphaMissense predicts ambiguous (score 0.3636) — an in-silico prediction, not a clinical call.

UNC80 p.Pro1823Ser

c.5467C>T · rs1023697059 · VCV1466166

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00274%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3636	ambiguous
REVEL	0.49	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 58 kb · p 4.4e-30 · regional, not allelic
Overall
CADD	25.9	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 P1757S vs ClinVar P1823S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00274% African / African-American · 2/73,016 alleles

Filtering AF 0.000455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000193% 3/1,551,536 alleles · very rare exomes 1/1,399,390 · genomes 2/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00274%	36,508
Admixed American	0.00196%	50,976

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.Pro1823Ser
Coding: c.5467C>T
MANE Select: NM_001371986
dbSNP: rs1023697059
Type: single nucleotide variant
Location: chr2:209921623 (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.Pro1823= Likely benign ★ same residue
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

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-pro1823ser (accessed [today's date]).

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