Is BTN2A2 p.Ser267Ala (c.799T>G) pathogenic?

BTN2A2 p.Ser267Ala (c.799T>G) is classified Benign in BTN2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-04). AlphaMissense: likely benign (0.0565); Low-frequency (popmax 1.68%, afr).

How common is BTN2A2 p.Ser267Ala (c.799T>G) in the general population?

BTN2A2 p.Ser267Ala (c.799T>G) is low-frequency (popmax 1.68%, afr) (gnomAD).

What do computational predictors say about BTN2A2 p.Ser267Ala (c.799T>G)?

AlphaMissense predicts likely benign (score 0.0565) — an in-silico prediction, not a clinical call.

BTN2A2 p.Ser267Ala

c.799T>G · rs113893469 · VCV720365

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0565 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.68%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0565	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -1.94	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 -0.63	GERP -0.91
Regional constraint	o/e 0.94	unconstrained · MANE · 9,142 bp · p 0.12 · regional, not allelic
Overall
CADD	0.013	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 1.68% African / African-American · 1,263/75,044 alleles

Filtering AF 1.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 0.101% 1,638/1,614,204 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.68%	59
Middle Eastern	0.578%	173
Admixed American	0.19%	527
Remaining individualsnot grpmax-eligible	0.136%	735
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,645
South Asian	0.0143%	7,006
European (non-Finnish)	0.00932%	10,728

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.Ser267Ala
Coding: c.799T>G
MANE Select: NM_006995
dbSNP: rs113893469
Type: single nucleotide variant
Location: chr6:26390079 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 1 PDB

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-ser267ala (accessed [today's date]).

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