Is BTRC p.Thr364= (c.1092G>A) pathogenic?

BTRC p.Thr364= (c.1092G>A) is classified Likely benign in BTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). Ultra-rare (popmax 0.0439%, nfe).

How common is BTRC p.Thr364= (c.1092G>A) in the general population?

BTRC p.Thr364= (c.1092G>A) is ultra-rare (popmax 0.0439%, nfe) (gnomAD).

BTRC p.Thr364=

c.1092G>A · rs61751508 · VCV2042943

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -5.1
Overall
CADD	1.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% European (non-Finnish) · 514/1,172,104 alleles

Filtering AF 0.0407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.0358% 574/1,604,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0469%	2,131
European (non-Finnish)grpmax	0.0439%	2,280
Remaining individualsnot grpmax-eligible	0.0289%	3,455
Admixed American	0.00835%	11,981
East Asian	0.0067%	14,925
African / African-American	0.00535%	18,679

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BTRC
Protein: p.Thr364=
Coding: c.1092G>A
MANE Select: NM_033637
dbSNP: rs61751508
Type: single nucleotide variant
Location: chr10:101533065 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.33 · 15 PDB
Residue 364: a β-strand

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

Similar variants

BTRC p.Thr364Met Uncertain significance ★ ⚠ same residue
BTRC p.Leu271Phe Uncertain significance ★★ ⚠ same type
BTRC p.Leu86Phe Uncertain significance ★★ ⚠ same type
BTRC c.556+7C>G Benign ★★ same type
BTRC p.Ala543Ser Benign ★★ same type
BTRC p.Ile229= Benign ★★ same type
BTRC p.Leu387= Likely benign ★★ same type
BTRC p.Pro592Arg Likely benign ★★ 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/btrc-p-thr364 (accessed [today's date]).

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