Is BUD23 p.Ser228Phe (c.683C>T) pathogenic?

BUD23 p.Ser228Phe (c.683C>T) is classified Uncertain significance in BUD23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.1873); Very rare (popmax 0.00017%, nfe).

How common is BUD23 p.Ser228Phe (c.683C>T) in the general population?

BUD23 p.Ser228Phe (c.683C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about BUD23 p.Ser228Phe (c.683C>T)?

AlphaMissense predicts likely benign (score 0.1873) — an in-silico prediction, not a clinical call.

BUD23 p.Ser228Phe

c.683C>T · rs2484524724 · VCV2536101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1873	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -7.93	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 4.6	GERP 6.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 14 kb · p 0.34 · regional, not allelic
Overall
CADD	20.2	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 0.00017% European (non-Finnish) · 2/1,179,124 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,458,190 alleles · very rare

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.Ser228Phe
Coding: c.683C>T
MANE Select: NM_017528
dbSNP: rs2484524724
Type: single nucleotide variant
Location: chr7:73694032 (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.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-ser228phe (accessed [today's date]).

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