Is BTRC p.Arg513Gln (c.1538G>A) pathogenic?

BTRC p.Arg513Gln (c.1538G>A) is classified Uncertain significance in BTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely pathogenic (0.9789); Very rare (popmax 0.0011%, sas).

How common is BTRC p.Arg513Gln (c.1538G>A) in the general population?

BTRC p.Arg513Gln (c.1538G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BTRC p.Arg513Gln (c.1538G>A)?

AlphaMissense predicts likely pathogenic (score 0.9789) — an in-silico prediction, not a clinical call.

BTRC p.Arg513Gln

c.1538G>A · VCV3993656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9789	likely pathogenic
REVEL	0.353	indeterminate
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 29 kb · p 5.9e-09 · regional, not allelic
Overall
CADD	34.0	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 0.0011% South Asian · 1/91,066 alleles

Overall 0.000137% 2/1,461,492 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	8.48e-05%	1,179,734

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.Arg513Gln
Coding: c.1538G>A
MANE Select: NM_033637
Type: single nucleotide variant
Location: chr10:101536614 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.33 · 15 PDB
Residue 513: 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-arg513gln (accessed [today's date]).

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