Is UNC80 p.Pro3234Ser (c.9700C>T) pathogenic?

UNC80 p.Pro3234Ser (c.9700C>T) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.0736); Very rare (popmax 0.00209%, nfe); Associated with Inborn genetic diseases.

What condition is associated with UNC80 p.Pro3234Ser (c.9700C>T)?

UNC80 p.Pro3234Ser (c.9700C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC80 p.Pro3234Ser (c.9700C>T) in the general population?

UNC80 p.Pro3234Ser (c.9700C>T) is very rare (popmax 0.00209%, nfe) (gnomAD).

What do computational predictors say about UNC80 p.Pro3234Ser (c.9700C>T)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

UNC80 p.Pro3234Ser

c.9700C>T · rs2471268558 · VCV3186696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00209%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.047	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 2.1	GERP 0.48, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,374 bp · p 0.24 · regional, not allelic
Overall
CADD	18.36	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P3168S vs ClinVar P3234S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00209% European (non-Finnish) · 24/1,146,006 alleles

Filtering AF 0.00142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00155% 24/1,549,746 alleles · very rare exomes 24/1,397,758 · genomes 0/151,988 · joint denominator

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.Pro3234Ser
Coding: c.9700C>T
MANE Select: NM_001371986
dbSNP: rs2471268558
Type: single nucleotide variant
Location: chr2:209994256 (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.Pro3234= 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-pro3234ser (accessed [today's date]).

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