Is UNC80 p.Pro609Ser (c.1825C>T) pathogenic?

UNC80 p.Pro609Ser (c.1825C>T) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). AlphaMissense: likely pathogenic (0.6352); Very rare (popmax 0.00196%, amr).

How common is UNC80 p.Pro609Ser (c.1825C>T) in the general population?

UNC80 p.Pro609Ser (c.1825C>T) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about UNC80 p.Pro609Ser (c.1825C>T)?

AlphaMissense predicts likely pathogenic (score 0.6352) — an in-silico prediction, not a clinical call.

UNC80 p.Pro609Ser

c.1825C>T · rs1188588782 · VCV2413229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6352 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.6352	likely pathogenic
REVEL	0.068	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.1	GERP 1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 57 kb · p 0.0051 · regional, not allelic
Overall
CADD	22.5	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

Grpmax group 0.00196% Admixed American · 1/51,000 alleles

Overall 6.44e-05% 1/1,552,210 alleles · very rare exomes 1/1,399,948 · genomes 0/152,262 · 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.Pro609Ser
Coding: c.1825C>T
MANE Select: NM_001371986
dbSNP: rs1188588782
Type: single nucleotide variant
Location: chr2:209819124 (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

Similar variants

UNC80 c.4110+1G>C Pathogenic/Likely pathogenic ★★ same type
UNC80 c.7287-1G>A Likely pathogenic ★★ same type
UNC80 c.8772+1G>A Likely pathogenic ★★ same type
UNC80 p.Arg1069Ter Pathogenic ★★ same type
UNC80 p.Arg1076Ter Pathogenic ★★ same type
UNC80 p.Arg1110Ter Pathogenic ★★ same type
UNC80 p.Arg1179Ter Pathogenic/Likely pathogenic ★★ same type
UNC80 p.Arg1285Ter Pathogenic ★★ same type

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-pro609ser (accessed [today's date]).

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