Is BTG3 p.Phe10Val (c.28T>G) pathogenic?

BTG3 p.Phe10Val (c.28T>G) is classified Uncertain significance in BTG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.781); Ultra-rare (popmax 0.0423%, eas).

How common is BTG3 p.Phe10Val (c.28T>G) in the general population?

BTG3 p.Phe10Val (c.28T>G) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

What do computational predictors say about BTG3 p.Phe10Val (c.28T>G)?

AlphaMissense predicts likely pathogenic (score 0.781) — an in-silico prediction, not a clinical call.

BTG3 p.Phe10Val

c.28T>G · rs200953650 · VCV2591105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.781	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 10 kb · p 1.6e-15 · regional, not allelic
Overall
CADD	27.0	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 0.0423% East Asian · 19/44,884 alleles

Filtering AF 0.0286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0276%

Overall 0.0253% 408/1,610,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,362
European (non-Finnish)	0.0313%	3,196
Remaining individualsnot grpmax-eligible	0.0208%	4,797
African / African-American	0.00536%	18,665
Admixed American	0.00339%	29,534
South Asian	0.00111%	89,908

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.Phe10Val
Coding: c.28T>G
MANE Select: NM_006806
dbSNP: rs200953650
Type: single nucleotide variant
Location: chr21:17609117 (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-phe10val (accessed [today's date]).

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