Is BTG3 p.Pro170Ala (c.508C>G) pathogenic?

BTG3 p.Pro170Ala (c.508C>G) is classified Uncertain significance in BTG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.0884); Very rare (popmax 0.01%, amr).

How common is BTG3 p.Pro170Ala (c.508C>G) in the general population?

BTG3 p.Pro170Ala (c.508C>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about BTG3 p.Pro170Ala (c.508C>G)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

BTG3 p.Pro170Ala

c.508C>G · VCV3262042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -7.12	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 4,582 bp · p 0.88 · regional, not allelic
Overall
CADD	21.5	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 0.01% Admixed American · 6/60,006 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000929% 15/1,613,860 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,001
African / African-American	0.00933%	10,713
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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: BTG3
Protein: p.Pro170Ala
Coding: c.508C>G
MANE Select: NM_006806
Type: single nucleotide variant
Location: chr21:17598628 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.61

Full BTG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTG3 c.311+603T>C Uncertain significance ★ same type
BTG3 c.311+622A>G Uncertain significance ★ same type
BTG3 c.311+624A>G Uncertain significance ★ same type
BTG3 c.311+632C>A Uncertain significance ★ same type
BTG3 c.311+637T>C Uncertain significance ★ same type
BTG3 c.311+646C>T Uncertain significance ★ same type
BTG3 c.311+661A>G Uncertain significance ★ same type
BTG3 c.311+679G>A 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/btg3-p-pro170ala (accessed [today's date]).

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