Is UNC80 p.Ser1359Pro (c.4075T>C) pathogenic?

UNC80 p.Ser1359Pro (c.4075T>C) is classified Conflicting classifications of pathogenicity in UNC80 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.055); Rare (popmax 0.138%, afr); Associated with Inborn genetic diseases.

What condition is associated with UNC80 p.Ser1359Pro (c.4075T>C)?

UNC80 p.Ser1359Pro (c.4075T>C) is associated with Inborn genetic diseases (ClinVar).

How common is UNC80 p.Ser1359Pro (c.4075T>C) in the general population?

UNC80 p.Ser1359Pro (c.4075T>C) is rare (popmax 0.138%, afr) (gnomAD).

What do computational predictors say about UNC80 p.Ser1359Pro (c.4075T>C)?

AlphaMissense predicts likely benign (score 0.055) — an in-silico prediction, not a clinical call.

UNC80 p.Ser1359Pro

c.4075T>C · rs61745161 · VCV1349235

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.055 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.055	likely benign
REVEL	0.058	moderately 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
Constraint at this position
Conservation	phyloP 5	GERP 2.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	19.37	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 S1361P vs ClinVar S1359P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% African / African-American · 101/73,162 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00838% 130/1,551,746 alleles · rare exomes 66/1,399,458 · genomes 64/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.138%	724
Admixed American	0.0333%	3,000
Remaining individualsnot grpmax-eligible	0.00831%	12,028
European (non-Finnish)	0.00061%	163,856

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.Ser1359Pro
Coding: c.4075T>C
MANE Select: NM_001371986
dbSNP: rs61745161
Type: single nucleotide variant
Location: chr2:209881059 (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.Ser1359= 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-ser1359pro (accessed [today's date]).

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