Is BTN2A2 p.Ala192Ser (c.574G>T) pathogenic?

BTN2A2 p.Ala192Ser (c.574G>T) is classified Likely benign in BTN2A2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-01). AlphaMissense: likely benign (0.0791); Rare (popmax 0.313%, mid); Associated with BTN2A2-related disorder.

What condition is associated with BTN2A2 p.Ala192Ser (c.574G>T)?

BTN2A2 p.Ala192Ser (c.574G>T) is associated with BTN2A2-related disorder (ClinVar).

How common is BTN2A2 p.Ala192Ser (c.574G>T) in the general population?

BTN2A2 p.Ala192Ser (c.574G>T) is rare (popmax 0.313%, mid) (gnomAD).

What do computational predictors say about BTN2A2 p.Ala192Ser (c.574G>T)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

BTN2A2 p.Ala192Ser

c.574G>T · rs144410497 · VCV3051820

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.313%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BTN2A2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.63	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 -5.9	GERP -3.7
Regional constraint	o/e 0.94	unconstrained · MANE · 9,142 bp · p 0.12 · regional, not allelic
Overall
CADD	0.031	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 0.313% Middle Eastern · 19/6,062 alleles

Filtering AF 0.262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.251%

Overall 0.0961% 1,552/1,614,184 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
Middle Easterngrpmax	0.313%	319
South Asian	0.291%	344
Admixed American	0.17%	589
Remaining individualsnot grpmax-eligible	0.123%	812
European (non-Finnish)	0.088%	1,136
East Asian	0.0379%	2,641
African / African-American	0.0173%	5,772
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,922
Finnishnot grpmax-eligible	0.0141%	7,114

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala192Ser
Coding: c.574G>T
MANE Select: NM_006995
dbSNP: rs144410497
Type: single nucleotide variant
Location: chr6:26388144 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 1 PDB
Residue 192: the ig-like c2-type domain

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

Disease context

BTN2A2-related disorder

Similar variants

BTN2A2 c.443-8C>G Likely benign same condition
BTN2A2 c.932-3C>T Likely benign same condition
BTN2A2 c.980-88G>C Benign same condition
BTN2A2 p.Ala336Thr Benign same condition
BTN2A2 p.Asn118= Likely benign same condition
BTN2A2 p.Gly203Ser Benign ⚠ same condition
BTN2A2 p.Leu19= Benign same condition
BTN2A2 p.Met506Thr Likely benign same condition

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-ala192ser (accessed [today's date]).

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