Is BTF3 p.Pro23Thr (c.67C>A) pathogenic?

BTF3 p.Pro23Thr (c.67C>A) is classified Uncertain significance in BTF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.0411%, afr).

How common is BTF3 p.Pro23Thr (c.67C>A) in the general population?

BTF3 p.Pro23Thr (c.67C>A) is ultra-rare (popmax 0.0411%, afr) (gnomAD).

What do computational predictors say about BTF3 p.Pro23Thr (c.67C>A)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

BTF3 p.Pro23Thr

c.67C>A · rs757317946 · VCV2229838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0411%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.41	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 1.5	GERP 2.8, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 520 bp · p 0.00067 · regional, not allelic
Overall
CADD	24.5	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 0.0411% African / African-American · 28/68,136 alleles

Filtering AF 0.0292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0251%

Overall 0.00188% 28/1,490,056 alleles · ultra-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: BTF3
Protein: p.Pro23Thr
Coding: c.67C>A
MANE Select: NM_001037637
dbSNP: rs757317946
Type: single nucleotide variant
Location: chr5:73498734 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.08 · 56 PDB
Residue 23: the 'disordered' region

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.Gln59Arg 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

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-pro23thr (accessed [today's date]).

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