Is BUD31 p.Tyr65Cys (c.194A>G) pathogenic?

BUD31 p.Tyr65Cys (c.194A>G) is classified Uncertain significance in BUD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: ambiguous (0.4228); Very rare (popmax 0.00602%, nfe).

How common is BUD31 p.Tyr65Cys (c.194A>G) in the general population?

BUD31 p.Tyr65Cys (c.194A>G) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about BUD31 p.Tyr65Cys (c.194A>G)?

AlphaMissense predicts ambiguous (score 0.4228) — an in-silico prediction, not a clinical call.

BUD31 p.Tyr65Cys

c.194A>G · rs191425967 · VCV2470053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4228	ambiguous
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -14.62	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.78, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 8,345 bp · p 0.0072 · regional, not allelic
Overall
CADD	29.4	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 0.00602% European (non-Finnish) · 71/1,179,850 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00446% 72/1,613,898 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,618
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Tyr65Cys
Coding: c.194A>G
MANE Select: NM_003910
dbSNP: rs191425967
Type: single nucleotide variant
Location: chr7:99416237 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 91.03 · 40 PDB
Residue 65: the 'interaction with ar' region; an α-helix

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

Similar variants

BUD31 p.Arg58Cys Uncertain significance ★ ⚠ same type
BUD31 p.Arg58His Uncertain significance ★ ⚠ same type
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

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-tyr65cys (accessed [today's date]).

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