Is UNC45A p.Arg431= (c.1291C>A) pathogenic?

UNC45A p.Arg431= (c.1291C>A) is classified Likely benign in UNC45A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Ultra-rare (popmax 0.0297%, sas).

How common is UNC45A p.Arg431= (c.1291C>A) in the general population?

UNC45A p.Arg431= (c.1291C>A) is ultra-rare (popmax 0.0297%, sas) (gnomAD).

UNC45A p.Arg431=

c.1291C>A · rs201875431 · VCV1896241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0297%, sas)

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 2.7	GERP -0.15, phastCons 1
Overall
CADD	12.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0297% South Asian · 27/91,028 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00198% 32/1,613,058 alleles · ultra-rare exomes 32/1,460,722 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0297%	3,371
Remaining individualsnot grpmax-eligible	0.00641%	15,602
East Asian	0.00223%	44,882

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.Arg431=
Coding: c.1291C>A
MANE Select: NM_018671
dbSNP: rs201875431
Type: single nucleotide variant
Location: chr15:90946705 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 431: 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.Arg431Trp Uncertain significance ★★ ⚠ same residue
UNC45A p.Arg431Gln 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

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-arg431 (accessed [today's date]).

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