Is BTRC p.Arg337Gln (c.1010G>A) pathogenic?

BTRC p.Arg337Gln (c.1010G>A) is classified Uncertain significance in BTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). AlphaMissense: likely benign (0.0586); Ultra-rare (popmax 0.0217%, amr).

How common is BTRC p.Arg337Gln (c.1010G>A) in the general population?

BTRC p.Arg337Gln (c.1010G>A) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about BTRC p.Arg337Gln (c.1010G>A)?

AlphaMissense predicts likely benign (score 0.0586) — an in-silico prediction, not a clinical call.

BTRC p.Arg337Gln

c.1010G>A · rs200759313 · VCV2185218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0586	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Pangolin	Δ0.20	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 29 kb · p 5.9e-09 · regional, not allelic
Overall
CADD	23.4	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 0.0217% Admixed American · 13/59,872 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0161% 259/1,612,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,606
European (non-Finnish)	0.0195%	5,128
Remaining individualsnot grpmax-eligible	0.0176%	5,676
South Asian	0.0033%	30,341
African / African-American	0.00268%	37,353

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.Arg337Gln
Coding: c.1010G>A
MANE Select: NM_033637
dbSNP: rs200759313
Type: single nucleotide variant
Location: chr10:101532983 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.33 · 15 PDB
Residue 337: a β-strand

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

Similar variants

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
BTRC p.Pro592His 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-arg337gln (accessed [today's date]).

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