Is UNC45A p.Ala362Pro (c.1084G>C) pathogenic?

UNC45A p.Ala362Pro (c.1084G>C) is classified Uncertain significance in UNC45A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-09). AlphaMissense: likely benign (0.0695); Very rare (popmax 0.000254%, nfe).

How common is UNC45A p.Ala362Pro (c.1084G>C) in the general population?

UNC45A p.Ala362Pro (c.1084G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about UNC45A p.Ala362Pro (c.1084G>C)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

UNC45A p.Ala362Pro

c.1084G>C · rs144297073 · VCV2188676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -3.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.8
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	0.006	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,584 alleles · very rare exomes 3/1,460,248 · genomes 0/152,336 · 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.Ala362Pro
Coding: c.1084G>C
MANE Select: NM_018671
dbSNP: rs144297073
Type: single nucleotide variant
Location: chr15:90944948 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 362: a UniProt-annotated variant site (in oohe; uncertain significance)

Full UNC45A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UNC45A p.Ala362Ser Uncertain significance ★ ⚠ same residue
UNC45A p.Ala362Val Uncertain significance ★ ⚠ same residue
UNC45A p.Ala362= Likely benign ★ same residue
UNC45A p.Ala362Thr Likely benign ★ same residue
UNC45A p.Ala214Val Uncertain significance ★★ ⚠ same type
UNC45A p.Ala371Thr Uncertain significance ★★ ⚠ same type
UNC45A p.Ala386Val Uncertain significance ★★ ⚠ same type
UNC45A p.Ala428Thr Uncertain significance ★★ ⚠ 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/unc45a-p-ala362pro (accessed [today's date]).

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