Is BUD23 p.Met187Val (c.559A>G) pathogenic?

BUD23 p.Met187Val (c.559A>G) is classified Likely benign in BUD23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely benign (0.0572); Ultra-rare (popmax 0.0165%, sas).

How common is BUD23 p.Met187Val (c.559A>G) in the general population?

BUD23 p.Met187Val (c.559A>G) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about BUD23 p.Met187Val (c.559A>G)?

AlphaMissense predicts likely benign (score 0.0572) — an in-silico prediction, not a clinical call.

BUD23 p.Met187Val

c.559A>G · VCV3993776

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0572 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0572	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -2.01	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 3	GERP 5.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 14 kb · p 0.34 · regional, not allelic
Overall
CADD	5.243	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,082 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00109% 16/1,461,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,072
European (non-Finnish)	8.47e-05%	1,180,018

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.Met187Val
Coding: c.559A>G
MANE Select: NM_017528
Type: single nucleotide variant
Location: chr7:73693377 (GRCh38)
Gene constraint: LOEUF 0.916 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 6 PDB
Residue 187: a β-strand

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

Similar variants

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
BUD23 p.Ala2Gly Uncertain significance ★ ⚠ same type
BUD23 p.Ala2Val 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-met187val (accessed [today's date]).

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