Is BTN3A1 p.Arg101Trp (c.301C>T) pathogenic?

BTN3A1 p.Arg101Trp (c.301C>T) is classified Uncertain significance in BTN3A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.1423); Ultra-rare (popmax 0.0314%, eas).

How common is BTN3A1 p.Arg101Trp (c.301C>T) in the general population?

BTN3A1 p.Arg101Trp (c.301C>T) is ultra-rare (popmax 0.0314%, eas) (gnomAD).

What do computational predictors say about BTN3A1 p.Arg101Trp (c.301C>T)?

AlphaMissense predicts likely benign (score 0.1423) — an in-silico prediction, not a clinical call.

BTN3A1 p.Arg101Trp

c.301C>T · VCV3482902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1423 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0314%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1423	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -8.99	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 -10	GERP -3.7
Regional constraint	o/e 0.56	unconstrained · MANE · 1,627 bp · p 2.8e-05 · regional, not allelic
Overall
CADD	16.14	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 0.0314% East Asian · 14/44,558 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0152%

Overall 0.00229% 36/1,569,624 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0314%	3,183
Admixed American	0.00859%	11,640
Ashkenazi Jewishnot grpmax-eligible	0.00688%	14,541
South Asian	0.00225%	44,411
African / African-American	0.00146%	68,528
European (non-Finnish)	0.00104%	95,956

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: BTN3A1
Protein: p.Arg101Trp
Coding: c.301C>T
MANE Select: NM_007048
Type: single nucleotide variant
Location: chr6:26406124 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66 · 44 PDB
Residue 101: the ig-like v-type 1 domain; a disulfide bond

Full BTN3A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTN3A1 p.Leu227His Likely benign ★★ ⚠ same type
BTN3A1 p.Ala251Ser Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala251Thr Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala294Ser Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala340Val Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala48Thr Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala91Thr Uncertain significance ★ ⚠ same type
BTN3A1 p.Arg315Lys 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/btn3a1-p-arg101trp (accessed [today's date]).

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