Is BTN2A2 p.Leu430Val (c.1288C>G) pathogenic?

BTN2A2 p.Leu430Val (c.1288C>G) is classified Uncertain significance in BTN2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely benign (0.1456); Ultra-rare (popmax 0.032%, afr).

How common is BTN2A2 p.Leu430Val (c.1288C>G) in the general population?

BTN2A2 p.Leu430Val (c.1288C>G) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about BTN2A2 p.Leu430Val (c.1288C>G)?

AlphaMissense predicts likely benign (score 0.1456) — an in-silico prediction, not a clinical call.

BTN2A2 p.Leu430Val

c.1288C>G · rs199832316 · VCV2238434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1456 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1456	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -7.95	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 0.34	GERP -0.14
Regional constraint	o/e 0.94	unconstrained · MANE · 9,142 bp · p 0.12 · regional, not allelic
Overall
CADD	15.8	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 0.032% African / African-American · 24/75,052 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0207%

Overall 0.021% 339/1,614,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,127
European (non-Finnish)	0.024%	4,170
East Asian	0.0201%	4,986
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.015%	6,670
South Asian	0.0022%	45,543
Finnishnot grpmax-eligible	0.00156%	64,040

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: BTN2A2
Protein: p.Leu430Val
Coding: c.1288C>G
MANE Select: NM_006995
dbSNP: rs199832316
Type: single nucleotide variant
Location: chr6:26392683 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 1 PDB
Residue 430: the b30.2/spry domain

Full BTN2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTN2A2 p.Ala147Gly Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala199Thr Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala201Pro Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala210Ser Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala248Glu Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala248Pro Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala254Thr Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala327Val 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/btn2a2-p-leu430val (accessed [today's date]).

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