Is UNC45A p.Ala409= (c.1227C>T) pathogenic?

UNC45A p.Ala409= (c.1227C>T) is classified Likely benign in UNC45A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). Rare (popmax 0.1%, eas).

How common is UNC45A p.Ala409= (c.1227C>T) in the general population?

UNC45A p.Ala409= (c.1227C>T) is rare (popmax 0.1%, eas) (gnomAD).

UNC45A p.Ala409=

c.1227C>T · rs200344405 · VCV1655124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.1%, eas)

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 -2.2	GERP -1.3
Overall
CADD	11.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% East Asian · 45/44,822 alleles

Filtering AF 0.0771% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0689%

Overall 0.00864% 139/1,609,562 alleles · rare exomes 125/1,457,232 · genomes 14/152,330 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.1%	996
European (non-Finnish)	0.00738%	13,543
South Asian	0.00331%	30,238
Remaining individualsnot grpmax-eligible	0.00322%	31,088
Admixed American	0.00167%	59,918
African / African-American	0.00133%	74,960

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.Ala409=
Coding: c.1227C>T
MANE Select: NM_018671
dbSNP: rs200344405
Type: single nucleotide variant
Location: chr15:90946641 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 409: 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.Ala409Val Uncertain significance ★ ⚠ 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
UNC45A p.Ala592Val Uncertain significance ★★ ⚠ same type
UNC45A p.Ala711Thr Uncertain significance ★★ ⚠ same type
UNC45A p.Ala761Thr 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-ala409 (accessed [today's date]).

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