Is UNC80 p.Pro1604Arg (c.4811C>G) pathogenic?

UNC80 p.Pro1604Arg (c.4811C>G) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely pathogenic (0.9055); Ultra-rare (popmax 0.0202%, sas); Associated with Inborn genetic diseases.

What condition is associated with UNC80 p.Pro1604Arg (c.4811C>G)?

UNC80 p.Pro1604Arg (c.4811C>G) is associated with Inborn genetic diseases (ClinVar).

How common is UNC80 p.Pro1604Arg (c.4811C>G) in the general population?

UNC80 p.Pro1604Arg (c.4811C>G) is ultra-rare (popmax 0.0202%, sas) (gnomAD).

What do computational predictors say about UNC80 p.Pro1604Arg (c.4811C>G)?

AlphaMissense predicts likely pathogenic (score 0.9055) — an in-silico prediction, not a clinical call.

UNC80 p.Pro1604Arg

c.4811C>G · VCV3466153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9055	likely pathogenic
REVEL	0.265	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 2.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	27.2	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 P1538R vs ClinVar P1604R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0202% South Asian · 17/84,014 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.00116% 18/1,551,208 alleles · ultra-rare exomes 16/1,399,098 · genomes 2/152,110 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0202%	4,942
Remaining individualsnot grpmax-eligible	0.00166%	60,134

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.Pro1604Arg
Coding: c.4811C>G
MANE Select: NM_001371986
Type: single nucleotide variant
Location: chr2:209912588 (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-pro1604arg (accessed [today's date]).

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