Is BUD23 p.Ala2Val (c.5C>T) pathogenic?

BUD23 p.Ala2Val (c.5C>T) is classified Uncertain significance in BUD23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.2226); Ultra-rare (popmax 0.0313%, eas).

How common is BUD23 p.Ala2Val (c.5C>T) in the general population?

BUD23 p.Ala2Val (c.5C>T) is ultra-rare (popmax 0.0313%, eas) (gnomAD).

What do computational predictors say about BUD23 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2226) — an in-silico prediction, not a clinical call.

BUD23 p.Ala2Val

c.5C>T · rs782291625 · VCV3135626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2226 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0313%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2226	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -9.34	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 4.8	GERP 6.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 14 kb · p 0.34 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0313% East Asian · 14/44,740 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0018% 29/1,609,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0313%	3,196
African / African-American	0.00267%	37,421
Remaining individualsnot grpmax-eligible	0.00161%	62,212
South Asian	0.0011%	90,848
European (non-Finnish)	0.000933%	107,136

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: BUD23
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_017528
dbSNP: rs782291625
Type: single nucleotide variant
Location: chr7:73683630 (GRCh38)
Gene constraint: LOEUF 0.916 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 6 PDB

Full BUD23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUD23 p.Ala2Gly Uncertain significance ★ ⚠ same residue
BUD23 p.Ala2= Likely benign ★ same residue
BUD23 p.Ala195= Benign ★★ same type
BUD23 c.702-107G>A Uncertain significance ★ same type
BUD23 c.702-129G>A Uncertain significance ★ same type
BUD23 c.702-93C>T Uncertain significance ★ same type
BUD23 p.Ala139Ser Uncertain significance ★ ⚠ same type
BUD23 p.Ala23Thr 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/bud23-p-ala2val (accessed [today's date]).

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