Is UNC45A p.Ile340= (c.1020C>T) pathogenic?

UNC45A p.Ile340= (c.1020C>T) is classified Benign in UNC45A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 16.2%, sas) — too common for a highly-penetrant pathogenic allele.

UNC45A p.Ile340=

Q: How common is UNC45A p.Ile340= (c.1020C>T) in the general population?

UNC45A p.Ile340= (c.1020C>T) is common (popmax 16.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1020C>T · rs8034551 · VCV1164964

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 16.2%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.49	GERP -1.4, phastCons 0.12
Overall
CADD	8.965	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.2% South Asian · 14,683/90,612 alleles

Filtering AF 16% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.9%

Overall 8.76% 141,044/1,610,210 alleles · common exomes 130,993/1,457,956 · genomes 10,051/152,254 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	16.2%	6
Amishnot grpmax-eligible	14.7%	7
European (non-Finnish)	9.26%	11
Finnishnot grpmax-eligible	9.22%	11
Remaining individualsnot grpmax-eligible	8.34%	12
Ashkenazi Jewishnot grpmax-eligible	7.97%	13
Middle Eastern	6.19%	16
Admixed American	3.77%	27
African / African-American	1.46%	69
East Asian	0.132%	760

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.Ile340=
Coding: c.1020C>T
MANE Select: NM_018671
dbSNP: rs8034551
Type: single nucleotide variant
Location: chr15:90943075 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 340: 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.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
UNC45A p.Arg107Gly 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-ile340 (accessed [today's date]).

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