Is TFE3 p.Arg9Pro (c.26G>C) pathogenic?

TFE3 p.Arg9Pro (c.26G>C) is classified Likely benign in TFE3 (ClinVar, Single submitter, 3 submitters). AlphaMissense: likely benign (0.0908); Low-frequency (popmax 1.15%, eas).

How common is TFE3 p.Arg9Pro (c.26G>C) in the general population?

TFE3 p.Arg9Pro (c.26G>C) is low-frequency (popmax 1.15%, eas) (gnomAD).

What do computational predictors say about TFE3 p.Arg9Pro (c.26G>C)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

TFE3 p.Arg9Pro

c.26G>C · rs782109836 · VCV1206125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.87	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 1.6	GERP 0.38, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,898 bp · p 0.79 · regional, not allelic
Overall
CADD	21.8	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

Grpmax group 1.15% East Asian · 365/31,735 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.0378% 444/1,173,835 alleles · low-frequency exomes 385/1,061,279 · genomes 59/112,556 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.15%	87
South Asian	0.0864%	1,158
Remaining individualsnot grpmax-eligible	0.0584%	1,714
European (non-Finnish)	0.000682%	146,604

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: TFE3
Protein: p.Arg9Pro
Coding: c.26G>C
MANE Select: NM_006521
dbSNP: rs782109836
Type: single nucleotide variant
Location: chrX:49043201 (GRCh38)
Structure: AlphaFold pLDDT 60.54 · 1 PDB

Full TFE3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TFE3 p.Arg117Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
TFE3 p.Thr187Met Pathogenic/Likely pathogenic ★★ same type
TFE3 p.Gly370Ser Uncertain significance ★★ ⚠ same type
TFE3 p.His509Asn Uncertain significance ★★ ⚠ same type
TFE3 p.Pro495Ser Uncertain significance ★★ ⚠ same type
TFE3 p.Ser153Pro Uncertain significance ★★ ⚠ same type
TFE3 p.Ser377Asn Uncertain significance ★★ ⚠ same type
TFE3 p.Val311Met 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/tfe3-p-arg9pro (accessed [today's date]).

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