Is UNC45A p.Phe587Ser (c.1760T>C) pathogenic?

UNC45A p.Phe587Ser (c.1760T>C) is classified Uncertain significance in UNC45A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely pathogenic (0.9277); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with UNC45A p.Phe587Ser (c.1760T>C)?

UNC45A p.Phe587Ser (c.1760T>C) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45A p.Phe587Ser (c.1760T>C) in the general population?

UNC45A p.Phe587Ser (c.1760T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about UNC45A p.Phe587Ser (c.1760T>C)?

AlphaMissense predicts likely pathogenic (score 0.9277) — an in-silico prediction, not a clinical call.

UNC45A p.Phe587Ser

c.1760T>C · rs749290193 · VCV2306719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9277 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9277	likely pathogenic
REVEL	0.688	pathogenic-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 6.2e-05% 1/1,614,054 alleles · very rare exomes 1/1,461,786 · genomes 0/152,268 · 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: UNC45A
Protein: p.Phe587Ser
Coding: c.1760T>C
MANE Select: NM_018671
dbSNP: rs749290193
Type: single nucleotide variant
Location: chr15:90948676 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 587: a UniProt-annotated variant site (in oohe; uncertain significance)

Full UNC45A 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

UNC45A p.Ala214Val Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala371Thr Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala386Val Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala428Thr Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala592Val Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala711Thr Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala761Thr Uncertain significance ★★ ⚠ same condition
UNC45A p.Arg107Gly 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/unc45a-p-phe587ser (accessed [today's date]).

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