Is UNC45A p.Ala498= (c.1494G>A) pathogenic?

UNC45A p.Ala498= (c.1494G>A) is classified Likely benign in UNC45A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). Very rare (popmax 0.00837%, amr); Associated with Inborn genetic diseases.

What condition is associated with UNC45A p.Ala498= (c.1494G>A)?

UNC45A p.Ala498= (c.1494G>A) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45A p.Ala498= (c.1494G>A) in the general population?

UNC45A p.Ala498= (c.1494G>A) is very rare (popmax 0.00837%, amr) (gnomAD).

UNC45A p.Ala498=

c.1494G>A · rs575944142 · VCV1585020

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00837%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4.1
Overall
CADD	0.527	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00837% Admixed American · 5/59,708 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00144% 23/1,599,894 alleles · very rare exomes 20/1,447,602 · genomes 3/152,292 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00837%	11,942
South Asian	0.00333%	30,075
Remaining individualsnot grpmax-eligible	0.00162%	61,806
African / African-American	0.00134%	74,842
European (non-Finnish)	0.00111%	89,958

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.Ala498=
Coding: c.1494G>A
MANE Select: NM_018671
dbSNP: rs575944142
Type: single nucleotide variant
Location: chr15:90946908 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 498: 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.Ala498Val Uncertain significance ★ ⚠ 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-ala498 (accessed [today's date]).

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