Is BTN2A2 p.Phe275Leu (c.825C>A) pathogenic?

BTN2A2 p.Phe275Leu (c.825C>A) is classified Likely benign in BTN2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely benign (0.3129); Ultra-rare (popmax 0.0512%, eas).

How common is BTN2A2 p.Phe275Leu (c.825C>A) in the general population?

BTN2A2 p.Phe275Leu (c.825C>A) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

What do computational predictors say about BTN2A2 p.Phe275Leu (c.825C>A)?

AlphaMissense predicts likely benign (score 0.3129) — an in-silico prediction, not a clinical call.

BTN2A2 p.Phe275Leu

c.825C>A · rs764083633 · VCV2603499

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3129 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3129	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.58	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 0.74	GERP -2, phastCons 0.1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,142 bp · p 0.12 · regional, not allelic
Overall
CADD	2.913	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 0.0512% East Asian · 23/44,900 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00149% 24/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,952
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Phe275Leu
Coding: c.825C>A
MANE Select: NM_006995
dbSNP: rs764083633
Type: single nucleotide variant
Location: chr6:26390105 (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-phe275leu (accessed [today's date]).

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