Is BTNL9 p.Pro504Leu (c.1511C>T) pathogenic?

BTNL9 p.Pro504Leu (c.1511C>T) is classified Uncertain significance in BTNL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.1288); Very rare (popmax 0.00669%, eas).

How common is BTNL9 p.Pro504Leu (c.1511C>T) in the general population?

BTNL9 p.Pro504Leu (c.1511C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about BTNL9 p.Pro504Leu (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.1288) — an in-silico prediction, not a clinical call.

BTNL9 p.Pro504Leu

c.1511C>T · rs141905608 · VCV3135575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1288	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	phastCons 0.029
Regional constraint	o/e 1.07	unconstrained · MANE · 14 kb · p 0.044 · regional, not allelic
Overall
CADD	12.36	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 0.00669% East Asian · 3/44,862 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00267% 43/1,611,368 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,954
African / African-American	0.004%	24,976
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,572
European (non-Finnish)	0.00297%	33,708
South Asian	0.0011%	91,010

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.Pro504Leu
Coding: c.1511C>T
MANE Select: NM_152547
dbSNP: rs141905608
Type: single nucleotide variant
Location: chr5:181059765 (GRCh38)
Gene constraint: LOEUF 1.325 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28
Residue 504: the b30.2/spry domain

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

Similar variants

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
BTNL9 p.Ala335Thr 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-pro504leu (accessed [today's date]).

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