Is BTN3A2 p.Pro193Arg (c.578C>G) pathogenic?

BTN3A2 p.Pro193Arg (c.578C>G) is classified Uncertain significance in BTN3A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely benign (0.0984); Very rare (popmax 0.00667%, afr).

How common is BTN3A2 p.Pro193Arg (c.578C>G) in the general population?

BTN3A2 p.Pro193Arg (c.578C>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about BTN3A2 p.Pro193Arg (c.578C>G)?

AlphaMissense predicts likely benign (score 0.0984) — an in-silico prediction, not a clinical call.

BTN3A2 p.Pro193Arg

c.578C>G · VCV3993599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0984	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -9.54	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 -5.3	GERP 0.68
Regional constraint	o/e 0.88	unconstrained · MANE · 4,036 bp · p 0.061 · regional, not allelic
Overall
CADD	17.25	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 0.00667% African / African-American · 5/74,938 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00328% 5/152,220 alleles · very rare

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: BTN3A2
Protein: p.Pro193Arg
Coding: c.578C>G
MANE Select: NM_007047
Type: single nucleotide variant
Location: chr6:26370466 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23 · 18 PDB
Residue 193: a disulfide bond; an α-helix

Full BTN3A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTN3A2 p.Ala110Thr Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala182Asp Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala192Val Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala233Gly Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala245Thr Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala264Thr Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala266Val Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala48Thr 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/btn3a2-p-pro193arg (accessed [today's date]).

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