Is UNC45A p.Ala322Val (c.965C>T) pathogenic?

UNC45A p.Ala322Val (c.965C>T) is classified Benign/Likely benign in UNC45A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.0679); Rare (popmax 0.795%, afr); Associated with Inborn genetic diseases.

What condition is associated with UNC45A p.Ala322Val (c.965C>T)?

UNC45A p.Ala322Val (c.965C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45A p.Ala322Val (c.965C>T) in the general population?

UNC45A p.Ala322Val (c.965C>T) is rare (popmax 0.795%, afr) (gnomAD).

What do computational predictors say about UNC45A p.Ala322Val (c.965C>T)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

UNC45A p.Ala322Val

c.965C>T · rs79604948 · VCV1170133

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.795%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -3.84	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 -0.086	GERP -1.3, phastCons 0.12
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	4.436	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 0.795% African / African-American · 597/75,058 alleles

Filtering AF 0.743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.722%

Overall 0.0676% 1,092/1,614,192 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.795%	126
Middle Eastern	0.33%	303
Admixed American	0.21%	476
Remaining individualsnot grpmax-eligible	0.186%	539
East Asian	0.0245%	4,080
European (non-Finnish)	0.0184%	5,438
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
South Asian	0.0022%	45,540

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.Ala322Val
Coding: c.965C>T
MANE Select: NM_018671
dbSNP: rs79604948
Type: single nucleotide variant
Location: chr15:90943020 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 322: 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.Ala322= Likely benign ★★ same residue
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

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-ala322val (accessed [today's date]).

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