Is BTNL9 p.Pro98Arg (c.293C>G) pathogenic?

BTNL9 p.Pro98Arg (c.293C>G) is classified Uncertain significance in BTNL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.0989); Very rare (popmax 0.00167%, amr).

How common is BTNL9 p.Pro98Arg (c.293C>G) in the general population?

BTNL9 p.Pro98Arg (c.293C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BTNL9 p.Pro98Arg (c.293C>G)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

BTNL9 p.Pro98Arg

c.293C>G · rs150556835 · VCV3135576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -8.94	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 -4.4	GERP -3.7
Regional constraint	o/e 1.07	unconstrained · MANE · 14 kb · p 0.044 · regional, not allelic
Overall
CADD	0.083	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000992% 16/1,613,432 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00119%	84,285

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: BTNL9
Protein: p.Pro98Arg
Coding: c.293C>G
MANE Select: NM_152547
dbSNP: rs150556835
Type: single nucleotide variant
Location: chr5:181048110 (GRCh38)
Gene constraint: LOEUF 1.325 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28
Residue 98: a disulfide bond; the ig-like v-type domain

Full BTNL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTNL9 p.Pro98Leu Uncertain significance ★ ⚠ same residue
BTNL9 p.Ala144Pro Uncertain significance ★ ⚠ same type
BTNL9 p.Ala200Val Uncertain significance ★ ⚠ same type
BTNL9 p.Ala252Val Uncertain significance ★ ⚠ same type
BTNL9 p.Ala261Thr Uncertain significance ★ ⚠ same type
BTNL9 p.Ala273Thr Uncertain significance ★ ⚠ same type
BTNL9 p.Ala291Glu Uncertain significance ★ ⚠ same type
BTNL9 p.Ala314Thr 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/btnl9-p-pro98arg (accessed [today's date]).

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