Is BTF3 p.Gln59Arg (c.176A>G) pathogenic?

BTF3 p.Gln59Arg (c.176A>G) is classified Uncertain significance in BTF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely pathogenic (0.8855); Absent from gnomAD v4.1.

How common is BTF3 p.Gln59Arg (c.176A>G) in the general population?

BTF3 p.Gln59Arg (c.176A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTF3 p.Gln59Arg (c.176A>G)?

AlphaMissense predicts likely pathogenic (score 0.8855) — an in-silico prediction, not a clinical call.

BTF3 p.Gln59Arg

c.176A>G · VCV3482853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8855	likely pathogenic
REVEL	0.265	benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5.2, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 520 bp · p 0.00067 · regional, not allelic
Overall
CADD	25.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BTF3
Protein: p.Gln59Arg
Coding: c.176A>G
MANE Select: NM_001037637
Type: single nucleotide variant
Location: chr5:73499177 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.08 · 56 PDB
Residue 59: an α-helix

Full BTF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTF3 p.Ala156Val Uncertain significance ★ ⚠ same type
BTF3 p.Arg13Trp Uncertain significance ★ ⚠ same type
BTF3 p.Arg71Cys Uncertain significance ★ ⚠ same type
BTF3 p.Asp185Glu Uncertain significance ★ ⚠ same type
BTF3 p.Gly183Arg Uncertain significance ★ ⚠ same type
BTF3 p.Gly24Glu Uncertain significance ★ ⚠ same type
BTF3 p.His137Leu Uncertain significance ★ ⚠ same type
BTF3 p.Leu143Pro 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/btf3-p-gln59arg (accessed [today's date]).

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