Is BUD31 p.Arg58Cys (c.172C>T) pathogenic?

BUD31 p.Arg58Cys (c.172C>T) is classified Uncertain significance in BUD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely pathogenic (0.9756); Very rare (popmax 0.00223%, eas).

How common is BUD31 p.Arg58Cys (c.172C>T) in the general population?

BUD31 p.Arg58Cys (c.172C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BUD31 p.Arg58Cys (c.172C>T)?

AlphaMissense predicts likely pathogenic (score 0.9756) — an in-silico prediction, not a clinical call.

BUD31 p.Arg58Cys

c.172C>T · VCV3826154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9756	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -14.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.85, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 8,345 bp · p 0.0072 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000682% 11/1,613,880 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,400
East Asiangrpmax	0.00223%	44,890
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000339%	294,986

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BUD31
Protein: p.Arg58Cys
Coding: c.172C>T
MANE Select: NM_003910
Type: single nucleotide variant
Location: chr7:99416215 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 91.03 · 40 PDB

Full BUD31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUD31 p.Arg58His Uncertain significance ★ ⚠ same residue
BUD31 p.Arg8Gln Uncertain significance ★ ⚠ same type
BUD31 p.Arg8Trp Uncertain significance ★ ⚠ same type
BUD31 p.Glu35Gly Uncertain significance ★ ⚠ same type
BUD31 p.Ile52Asn Uncertain significance ★ ⚠ same type
BUD31 p.Met29Thr Uncertain significance ★ ⚠ same type
BUD31 p.Tyr65Cys 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/bud31-p-arg58cys (accessed [today's date]).

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