Is BTN2A2 p.Ala4Val (c.11C>T) pathogenic?

BTN2A2 p.Ala4Val (c.11C>T) is classified Benign in BTN2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-03). AlphaMissense: likely benign (0.1513); Low-frequency (popmax 2.78%, afr).

How common is BTN2A2 p.Ala4Val (c.11C>T) in the general population?

BTN2A2 p.Ala4Val (c.11C>T) is low-frequency (popmax 2.78%, afr) (gnomAD).

What do computational predictors say about BTN2A2 p.Ala4Val (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1513) — an in-silico prediction, not a clinical call.

BTN2A2 p.Ala4Val

c.11C>T · rs73736234 · VCV790029

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1513 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.78%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1513	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.30	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 -0.23	GERP 0.023
Regional constraint	o/e 0.94	unconstrained · MANE · 9,142 bp · p 0.12 · regional, not allelic
Overall
CADD	13.43	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 2.78% African / African-American · 2,081/74,986 alleles

Filtering AF 2.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.725% 11,699/1,614,050 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.78%	36
Ashkenazi Jewishnot grpmax-eligible	1.28%	78
Admixed American	1%	100
Remaining individualsnot grpmax-eligible	0.848%	118
Middle Eastern	0.841%	119
European (non-Finnish)	0.668%	150
Finnishnot grpmax-eligible	0.192%	521
South Asian	0.056%	1,786
East Asian	0.00446%	22,432

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.Ala4Val
Coding: c.11C>T
MANE Select: NM_006995
dbSNP: rs73736234
Type: single nucleotide variant
Location: chr6:26383832 (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-ala4val (accessed [today's date]).

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